Congestive heart failure with preserved EF pharmacotherapy: Difference between revisions

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Latest revision as of 15:31, 19 August 2022

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Seyedmahdi Pahlavani, M.D. [3] Edzel Lorraine Co, DMD, MD [4]

Overview

Heart failure has been divided into three subgroups including heart failure reduced ejection fraction, heart failure mildly reduced EF, heart failure preserved EF. HFrEF is defined when LVEF≤ 40% and significant LV systolic dysfunction. Patients with a LVEF between 41% and 49% have mildly reduced LV systolic function or HFmrEF. Patients with ejection fractions between 40-50% may benefit from similar therapies to those with LVEF≤ 40%. HFpEF is explained in the presence of symptoms and signs of HF, and evidence of structural and/or functional cardiac abnormalities and/or raised natriuretic peptides (NPs), and LVEF≥ 50%. Patients with non-cardiovascular disease including anaemia, pulmonary, renal, thyroid, or hepatic disease may mimic symptoms and signs of HF, but in the absence of cardiac dysfunction, they are not diagnosed for HF. Neverthless, these disorders can coexist with HF and exacerbate the HF syndrome.

Heart failure mildly reduced ejection fraction (HPmrEF), EF (41-49%)

The diagnosis of heart failure with mildly reduced ejection fraction

The diagnosis of HFmrEF requires the presence of symptoms and/or signs of HF, and a mildly reduced EF (41-49%) The presence of elevated NPs (BNP ≥35 pg/mL or NT-proBNP ≥125 pg/mL) and other evidence of structural heart disease including increased left atrial (LA) size, LVH or echocardiographic measures of LV filling.^[1]

Clinical characteristics

Clinical characteristics, risk factors, patterns of cardiac remodelling are similar to other subgroups of HF.
HFmrEF is more common in men, younger, and are more likely to have CAD (50-60%) and less likely to have AF and non-cardiac comorbidities. ambulatory
HFmrEF have lower mortality rate than those with HFrEF.

Treatment

Angiotensin-converting enzyme inhibitors

ACE-I may be considered in patients with HFmrEF and underlying CAD, hypertension, or post-MI LV systolic dysfunction.

Angiotensin receptor II type 1 receptor blockers

Candesartan reduced the number of patients hospitalized for HF among those with HFmrEF.^[2]
Treatment with ARBs may be considered in patients with HFmrEF patients with other cardiovascular indications.

Beta-blockers

Treatment with beta-blockers may be considered in patients with HFmrEF and another cardiovascular indications, such as AF or angina.^[3]

Mineralocorticoid receptor antagonists

In a retrospective analysis of the TOPCAT trial in patients with LVEF ≥45%, spironolactone reduced hospitalizations for HF in patients with an LVEF <55%.
Treatment with an MRA may be considered in patients with HFmrEF.

Angiotensin receptor-neprilysin inhibitor

Analysis of the PARADIGM-HF and PARAGON-HF trials showed that sacubitril/valsartan, compared to other forms of RAAS blockade reduced hospitalizations in patients with HFmrEF.

Other drugs

In the DIG trial, use of digoxin for patients with HFmrEF in sinus rhythm was associated with fewer hospitalizations but no reduction in mortality and a trend to increase of cardiovascular deaths.
Therefore, there are insufficient data to recommend its use.
There are insufficient data on ivabradine in HFmrEF.

Devices

There is insufficient evidence regarding CRT or ICD therapy in patients with HFmrEF.

Medications indicated in patients with New York Heart Association (NYHA class II–IV) HFmrEF (heart failure with mildly reduced ejection fraction) (LVEF41-49%)

Recommedation for patients with NYHA class 2-4 heart failure with mildly reduced ejection fraction

Diuretics (Class I, Level of Evidence C):

❑ Diuretics are recommended in patients with congestion and HFmrEF in order reduce symptoms and signs

ACEI (Class IIb, Level of Evidence C):

❑ ACE-I may be considered for patients with HFmrEF to reduce the risk of HF hospitalization and death
❑ ARB may be indicated for patients with HFmrEF to reduce the risk of HF hospitalization and death
❑ Beta-blocker may be considered for patients with HFmrEF to reduce the risk of HF hospitalization and death,
❑ MRA may be considered for patients with HFmrEF to reduce the risk of HF hospitalization and death
❑Sacubitril/valsartan may be considered for patients with HFmrEF to reduce the risk of HF hospitalization and death

The above table adopted from 2021 ESC Guideline

^[4]

Class IIa
"1. In patients with HFmrEF, SGLT2i can be beneficial in decreasing HF hospitalizations and cardiovascular mortality. ^[5] (Level of Evidence: B-R) "

Class IIb
"2. Among patients with current or previous symptomatic HFmrEF (LVEF, 41%-49%), use of evidence-based beta blockers for HFrEF, ARNi, ACEi, or ARB, and MRAs may be considered to reduce the risk of HF hospitalization and cardiovascular mortality, particularly among patients with LVEF on the lower end of this spectrum. ^[6]^[7]^[8]^[9]^[10]^[1]^[11]^[12] (Level of Evidence: B-NR) "

The above table adopted from 2022 AHA Guideline

^[13]

Heart failure With Improved Ejection Fraction (HFimpEF)

Medications can cause improvement in symptoms, functional capacity, LVEF, and reverse remodeling in patients with HFrEF.
However, in most patients, LV function and structural abnormalities do not normalize completely, and symptoms and biomarker abnormalities may persist or reoccur.
Relapse may occur after withdrawal of medication despite the period of recovery from heart failure symptoms and improvement in LVEF. Therefore, maintaining the medications is necessary.
In an open-label RCT, discontinuation of HF medications in known cases of dilated cardiomyopathy—who were now asymptomatic, improved LVEF from <40% to ≥50%, normal left ventricular end-diastolic volume (LVEDV), NT-proBNP concentration <250 ng/L— caused in relapse of cardiomyopathy and HF in 40% of the patients within 6 months.^[8]
Definition of relapse (at least 1 of these):
A reduction in LVEF by >10% and <50%
An increase in LVEDV by >10% and to higher than the normal range
A 2-fold rise in NT-proBNP concentration and to >400 ng/L
Clinical evidence of HF.

Class I
"1. In patients with HFimpEF after treatment, medical therapy should be continued to prevent relapse of HF and LV dysfunction, even in patients who may become asymptomatic. ^[8] (Level of Evidence: B-R) "

The above tables adopted from 2022 AHA Guideline

^[13]

Heart failure preserved ejection fraction (HFpEF)

Clinical characteristics

HFpEF patients are older and more often female.
Atrial fibrillation (AF), chronic kidney disease (CKD), and non-cardiovascular comorbidities are more common in patients with HFpEF.^[14]
It is important to exclude other conditions that might mimic the HFpEF syndrome including lung disease, anaemia, obesity, and deconditioning.

The diagnosis of heart failure preserved ejection fraction

Echocardiographic criteria:
LA size (LA volume index >32 mL/m2)
Mitral E velocity <90 cm/s
Septal e' velocity <9 cm/s
E/e' ratio >9
The diagnosis is made when there are the following:

(1) Symptoms and signs of HF
(2) An LVEF ≥ 50%
(3) Evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/ raised LV filling pressures, including raised NPs

In the presence of AF, the threshold for LA volume index is >40 mL/m2
Exercise stress thresholds include E/e' ratio at peak stress ≥ 15 or tricuspid regurgitation (TR) velocity at peak stress >3.4 m/s
LV global longitudinal strain <16%

An invasively measured pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg (at rest) or ≥25 mmHg (with exercise) or LV end-diastolic pressure ≥16 mmHg (at rest) is generally considered diagnostic.^[15]
In the presence of non-invasive markers of raised LV filling pressures, the probability of a diagnosis of HFpEF increases.^[16]
No treatment has been shown to reduce mortality and morbidity in patients with HFpEF.
Hospitalizations for HF were reduced by candesartan and spironolactone, sacubitril/valsartan.
Many of HFpEF patients have underlying hypertension and/or CAD, treated with ACE-I/ARB, beta-blockers, or MRAs.
The Food and Drug Administration (FDA) has confirmed the use of sacubitril/valsartan and spironolactone in those with an LVEF ‘less than normal’.
These statements relate to patients within both the HFmrEF and HFpEF categories.
For sacubitril/valsartan, subgroup analysis from the PARAGON-HF study showed a reduction in HF hospitalizations in patients with LVEF <57%, and a meta-analysis of the PARADIGM-HF and PARAGON-HF studies showed a reduction in cardiovascular death and HF hospitalization in patients with LVEF below the normal range.
Use of spironolactone, in TOPCAT study was associated with reduced cardiovascular death and HF hospitalization,
Treatment should be aimed at reducing symptoms of congestion with diuretics such as loop diuretic.
Thiazide diuretics may be useful for managing hypertension.
Reducing body weight in obese patients and increasing exercise may further improve symptoms and exercise capacity.
Notably in patients with HFpEF, treatment of underlying risk factors, etiology, and coexisting comorbidities such as hypertension, CAD, AF, valvular heart disease are recommended.

Diuretic as needed (class1)

SGLT2i (class 2a)

MRA (class 2b)

Symptomatic heart failure with LVEF ≥ 50%

ARNi (class 2b)

ARB class 2b

The above tables adopted from 2022 AHA Guideline

^[13]

Recommedation for treatment of patients with HFpEF (heart failure preserved ejection fraction)

(Class I, Level of Evidence C):

❑ Screening, treatment, investigation of underlying etiologies, and cardiovascular and non-cardiovascular comorbidities is recommended in patients with HFpEF
❑Diuretics are recommended in congested patients with HFpEF to improve symptoms and signs

The above table adopted from 2021 ESC Guideline

^[4]

Class I
"1. Patients with HFpEF and hypertension should have medication titrated to attain blood pressure targets in accordance with published clinical practice guidelines to prevent morbidity. ^[17]^[18]^[19] (Level of Evidence: C-LD) "

Class IIa
"2. In patients with HFpEF, SGLT2i can be beneficial in decreasing HF hospitalizations and cardiovascular mortality. ^[5] (Level of Evidence:B-R) "
"3. In patients with HFpEF, management of AF can be useful to improve symptoms. (Level of Evidence: C-EO) "

Class IIb
"4. In selected patients with HFpEF, MRAs may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum. ^[20]^[21]^[10] (Level of Evidence:B-R) "
"5. In selected patients with HFpEF, the use of ARB may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum. ^[2]^[22](Level of Evidence: B-R) "
"6. In selected patients with HFpEF, ARNi may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum. ^[7]^[11](Level of Evidence: B-R) "

Class III (No Benefit)
"7. In patients with HFpEF, routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or QOL is ineffective. ^[23]^[24] (Level of Evidence:B-R) "

The above tables adopted from 2022 AHA Guideline

^[13]

External Link

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines^[25]

References

↑ ^1.0 ^1.1 Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, Abe R, Oikawa T, Kasahara S, Sato M, Shiroto T, Takahashi J, Miyata S, Shimokawa H (October 2017). "Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study". Eur J Heart Fail. 19 (10): 1258–1269. doi:10.1002/ejhf.807. PMID 28370829.
↑ ^2.0 ^2.1 Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J (September 2003). "Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial". Lancet. 362 (9386): 777–81. doi:10.1016/S0140-6736(03)14285-7. PMID 13678871.
↑ Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA (February 2005). "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 (3): 215–25. doi:10.1093/eurheartj/ehi115. PMID 15642700.
↑ ^4.0 ^4.1 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland J, Coats A, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam C, Lyon AR, McMurray J, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano G, Ruschitzka F, Kathrine Skibelund A (September 2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check |pmid= value (help). Vancouver style error: initials (help)
↑ ^5.0 ^5.1 Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M; et al. (2021). "Empagliflozin in Heart Failure with a Preserved Ejection Fraction". N Engl J Med. 385 (16): 1451–1461. doi:10.1056/NEJMoa2107038. PMID 34449189 Check |pmid= value (help). Review in: Ann Intern Med. 2022 Jan;175(1):JC4
↑ Cleland JGF, Bunting KV, Flather MD, Altman DG, Holmes J, Coats AJS; et al. (2018). "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 (1): 26–35. doi:10.1093/eurheartj/ehx564. PMC 5837435. PMID 29040525.
↑ ^7.0 ^7.1 Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP; et al. (2019). "Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction". N Engl J Med. 381 (17): 1609–1620. doi:10.1056/NEJMoa1908655. PMID 31475794.
↑ ^8.0 ^8.1 ^8.2 Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S; et al. (2019). "Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial". Lancet. 393 (10166): 61–73. doi:10.1016/S0140-6736(18)32484-X. PMC 6319251. PMID 30429050. Review in: Ann Intern Med. 2019 Mar 19;170(6):JC28
↑ Nilsson BB, Lunde P, Grøgaard HK, Holm I (2018). "Long-Term Results of High-Intensity Exercise-Based Cardiac Rehabilitation in Revascularized Patients for Symptomatic Coronary Artery Disease". Am J Cardiol. 121 (1): 21–26. doi:10.1016/j.amjcard.2017.09.011. PMID 29096886.
↑ ^10.0 ^10.1 Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K; et al. (2016). "Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial". Circ Heart Fail. 9 (3): e002744. doi:10.1161/CIRCHEARTFAILURE.115.002744. PMID 26915374.
↑ ^11.0 ^11.1 Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K; et al. (2020). "Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure". Circulation. 141 (5): 352–361. doi:10.1161/CIRCULATIONAHA.119.044586. PMID 31736342. Review in: Ann Intern Med. 2020 Jun 16;172(12):JC65
↑ Zheng SL, Chan FT, Nabeebaccus AA, Shah AM, McDonagh T, Okonko DO; et al. (2018). "Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis". Heart. 104 (5): 407–415. doi:10.1136/heartjnl-2017-311652. PMC 5861385. PMID 28780577. Review in: Ann Intern Med. 2017 Dec 19;167(12):JC68
↑ ^13.0 ^13.1 ^13.2 ^13.3 Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e876–e894. doi:10.1161/CIR.0000000000001062. PMID 35363500 Check |pmid= value (help).
↑ Borlaug BA (September 2020). "Evaluation and management of heart failure with preserved ejection fraction". Nat Rev Cardiol. 17 (9): 559–573. doi:10.1038/s41569-020-0363-2. PMID 32231333 Check |pmid= value (help).
↑ Barandiarán Aizpurua A, Sanders-van Wijk S, Brunner-La Rocca HP, Henkens M, Heymans S, Beussink-Nelson L, Shah SJ, van Empel V (March 2020). "Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction". Eur J Heart Fail. 22 (3): 413–421. doi:10.1002/ejhf.1614. PMID 31472035. Vancouver style error: initials (help)
↑ Ho JE, Zern EK, Wooster L, Bailey CS, Cunningham T, Eisman AS, Hardin KM, Zampierollo GA, Jarolim P, Pappagianopoulos PP, Malhotra R, Nayor M, Lewis GD (July 2019). "Differential Clinical Profiles, Exercise Responses, and Outcomes Associated With Existing HFpEF Definitions". Circulation. 140 (5): 353–365. doi:10.1161/CIRCULATIONAHA.118.039136. PMID 31132875.
↑ Thomopoulos C, Parati G, Zanchetti A (2016). "Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials". J Hypertens. 34 (10): 1921–32. doi:10.1097/HJH.0000000000001052. PMID 27454050.
↑ Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM; et al. (2016). "Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial". JAMA. 315 (24): 2673–82. doi:10.1001/jama.2016.7050. PMC 4988796. PMID 27195814. Review in: Ann Intern Med. 2016 Aug 16;165(4):JC14 Review in: Evid Based Med. 2017 Mar;22(1):30
↑ SPRINT Research Group. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM; et al. (2015). "A Randomized Trial of Intensive versus Standard Blood-Pressure Control". N Engl J Med. 373 (22): 2103–16. doi:10.1056/NEJMoa1511939. PMC 4689591. PMID 26551272. Review in: Ann Intern Med. 2016 Feb 16;164(4):JC15 Review in: Evid Based Med. 2016 Jun;21(3):101
↑ Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B; et al. (2014). "Spironolactone for heart failure with preserved ejection fraction". N Engl J Med. 370 (15): 1383–92. doi:10.1056/NEJMoa1313731. PMID 24716680. Review in: Ann Intern Med. 2014 Oct 21;161(8):JC6
↑ Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N; et al. (2015). "Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial". Circulation. 131 (1): 34–42. doi:10.1161/CIRCULATIONAHA.114.013255. PMID 25406305.
↑ Lund LH, Claggett B, Liu J, Lam CS, Jhund PS, Rosano GM; et al. (2018). "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 (8): 1230–1239. doi:10.1002/ejhf.1149. PMID 29431256.
↑ Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH; et al. (2015). "Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction". N Engl J Med. 373 (24): 2314–24. doi:10.1056/NEJMoa1510774. PMC 4712067. PMID 26549714.
↑ Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G; et al. (2013). "Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial". JAMA. 309 (12): 1268–77. doi:10.1001/jama.2013.2024. PMC 3835156. PMID 23478662.
↑ Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (May 2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e895–e1032. doi:10.1161/CIR.0000000000001063. PMID 35363499 Check |pmid= value (help).

Template:WikiDoc Sources

[pmid28370829-1] 1.0 ^1.1 Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, Abe R, Oikawa T, Kasahara S, Sato M, Shiroto T, Takahashi J, Miyata S, Shimokawa H (October 2017). "Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study". Eur J Heart Fail. 19 (10): 1258–1269. doi:10.1002/ejhf.807. PMID 28370829.

[pmid13678871-2] 2.0 ^2.1 Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J (September 2003). "Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial". Lancet. 362 (9386): 777–81. doi:10.1016/S0140-6736(03)14285-7. PMID 13678871.

[pmid15642700-3] Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA (February 2005). "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 (3): 215–25. doi:10.1093/eurheartj/ehi115. PMID 15642700.

[pmid34447992-4] 4.0 ^4.1 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland J, Coats A, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam C, Lyon AR, McMurray J, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano G, Ruschitzka F, Kathrine Skibelund A (September 2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check |pmid= value (help). Vancouver style error: initials (help)

[pmid34449189-5] 5.0 ^5.1 Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M; et al. (2021). "Empagliflozin in Heart Failure with a Preserved Ejection Fraction". N Engl J Med. 385 (16): 1451–1461. doi:10.1056/NEJMoa2107038. PMID 34449189 Check |pmid= value (help). Review in: Ann Intern Med. 2022 Jan;175(1):JC4

[pmid29040525-6] Cleland JGF, Bunting KV, Flather MD, Altman DG, Holmes J, Coats AJS; et al. (2018). "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 (1): 26–35. doi:10.1093/eurheartj/ehx564. PMC 5837435. PMID 29040525.

[pmid31475794-7] 7.0 ^7.1 Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP; et al. (2019). "Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction". N Engl J Med. 381 (17): 1609–1620. doi:10.1056/NEJMoa1908655. PMID 31475794.

[pmid30429050-8] 8.0 ^8.1 ^8.2 Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S; et al. (2019). "Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial". Lancet. 393 (10166): 61–73. doi:10.1016/S0140-6736(18)32484-X. PMC 6319251. PMID 30429050. Review in: Ann Intern Med. 2019 Mar 19;170(6):JC28

[pmid29096886-9] Nilsson BB, Lunde P, Grøgaard HK, Holm I (2018). "Long-Term Results of High-Intensity Exercise-Based Cardiac Rehabilitation in Revascularized Patients for Symptomatic Coronary Artery Disease". Am J Cardiol. 121 (1): 21–26. doi:10.1016/j.amjcard.2017.09.011. PMID 29096886.

[pmid26915374-10] 10.0 ^10.1 Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K; et al. (2016). "Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial". Circ Heart Fail. 9 (3): e002744. doi:10.1161/CIRCHEARTFAILURE.115.002744. PMID 26915374.

[pmid31736342-11] 11.0 ^11.1 Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K; et al. (2020). "Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure". Circulation. 141 (5): 352–361. doi:10.1161/CIRCULATIONAHA.119.044586. PMID 31736342. Review in: Ann Intern Med. 2020 Jun 16;172(12):JC65

[pmid28780577-12] Zheng SL, Chan FT, Nabeebaccus AA, Shah AM, McDonagh T, Okonko DO; et al. (2018). "Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis". Heart. 104 (5): 407–415. doi:10.1136/heartjnl-2017-311652. PMC 5861385. PMID 28780577. Review in: Ann Intern Med. 2017 Dec 19;167(12):JC68

[pmid35363500-13] 13.0 ^13.1 ^13.2 ^13.3 Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e876–e894. doi:10.1161/CIR.0000000000001062. PMID 35363500 Check |pmid= value (help).

[pmid32231333-14] Borlaug BA (September 2020). "Evaluation and management of heart failure with preserved ejection fraction". Nat Rev Cardiol. 17 (9): 559–573. doi:10.1038/s41569-020-0363-2. PMID 32231333 Check |pmid= value (help).

[pmid31472035-15] Barandiarán Aizpurua A, Sanders-van Wijk S, Brunner-La Rocca HP, Henkens M, Heymans S, Beussink-Nelson L, Shah SJ, van Empel V (March 2020). "Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction". Eur J Heart Fail. 22 (3): 413–421. doi:10.1002/ejhf.1614. PMID 31472035. Vancouver style error: initials (help)

[pmid31132875-16] Ho JE, Zern EK, Wooster L, Bailey CS, Cunningham T, Eisman AS, Hardin KM, Zampierollo GA, Jarolim P, Pappagianopoulos PP, Malhotra R, Nayor M, Lewis GD (July 2019). "Differential Clinical Profiles, Exercise Responses, and Outcomes Associated With Existing HFpEF Definitions". Circulation. 140 (5): 353–365. doi:10.1161/CIRCULATIONAHA.118.039136. PMID 31132875.

[pmid27454050-17] Thomopoulos C, Parati G, Zanchetti A (2016). "Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials". J Hypertens. 34 (10): 1921–32. doi:10.1097/HJH.0000000000001052. PMID 27454050.

[pmid27195814-18] Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM; et al. (2016). "Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial". JAMA. 315 (24): 2673–82. doi:10.1001/jama.2016.7050. PMC 4988796. PMID 27195814. Review in: Ann Intern Med. 2016 Aug 16;165(4):JC14 Review in: Evid Based Med. 2017 Mar;22(1):30

[pmid26551272-19] SPRINT Research Group. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM; et al. (2015). "A Randomized Trial of Intensive versus Standard Blood-Pressure Control". N Engl J Med. 373 (22): 2103–16. doi:10.1056/NEJMoa1511939. PMC 4689591. PMID 26551272. Review in: Ann Intern Med. 2016 Feb 16;164(4):JC15 Review in: Evid Based Med. 2016 Jun;21(3):101

[pmid24716680-20] Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B; et al. (2014). "Spironolactone for heart failure with preserved ejection fraction". N Engl J Med. 370 (15): 1383–92. doi:10.1056/NEJMoa1313731. PMID 24716680. Review in: Ann Intern Med. 2014 Oct 21;161(8):JC6

[pmid25406305-21] Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N; et al. (2015). "Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial". Circulation. 131 (1): 34–42. doi:10.1161/CIRCULATIONAHA.114.013255. PMID 25406305.

[pmid29431256-22] Lund LH, Claggett B, Liu J, Lam CS, Jhund PS, Rosano GM; et al. (2018). "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 (8): 1230–1239. doi:10.1002/ejhf.1149. PMID 29431256.

[pmid26549714-23] Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH; et al. (2015). "Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction". N Engl J Med. 373 (24): 2314–24. doi:10.1056/NEJMoa1510774. PMC 4712067. PMID 26549714.

[pmid23478662-24] Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G; et al. (2013). "Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial". JAMA. 309 (12): 1268–77. doi:10.1001/jama.2013.2024. PMC 3835156. PMID 23478662.

[pmid35363499-25] Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (May 2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e895–e1032. doi:10.1161/CIR.0000000000001063. PMID 35363499 Check |pmid= value (help).

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@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Congestive heart failure}}
-{{CMG}};{{AE}}{{MehdiP}}
+{{CMG}};{{AE}} {{Sara.Zand}} {{MehdiP}} {{EdzelCo}}
 ==Overview==
-Treatment of HFpEF is focused on treating underlying disease, such as [[hypertension]], [[Coronary heart disease|coronary artery disease]] and [[atrial fibrillation]]. [[Diuretics]] are the mainstay of [[pharmacotherapy]]. Other effective measures to control HFpEF include exercise, [[weight]] control and [[lipid]] control.
+[[Heart failure]] has been divided into three subgroups including [[heart failure reduced ejection fraction]], [[heart failure mildly reduced EF]], [[heart failure preserved EF]]. [[HFrEF]] is defined when [[LVEF]]≤ 40% and significant [[LV systolic dysfunction]]. [[Patients]] with a [[LVEF]] between 41% and 49% have [[ mildly reduced LV systolic function]] or [[HFmrEF]]. [[Patients]] with [[ejection fractions]] between 40-50%  may benefit from similar therapies to those with [[LVEF]]≤ 40%. [[HFpEF]] is explained in the presence of  symptoms and signs of [[HF]], and evidence of structural and/or functional [[cardiac]] abnormalities and/or raised [[natriuretic peptides]] ([[NPs]]), and [[LVEF]]≥ 50%. [[Patients]] with non-[[cardiovascular]] disease including [[anaemia]], [[pulmonary]], [[renal]], [[thyroid]], or [[hepatic]] disease may mimic symptoms and signs of [[HF]], but in the absence of [[cardiac]] dysfunction, they are not diagnosed for [[HF]]. Neverthless, these [[disorders]] can coexist with [[HF]] and exacerbate the [[HF]] syndrome.
 == [[Heart failure mildly reduced ejection fraction]]  ([[HPmrEF]]), [[EF]] (41-49%) ==
 ===The diagnosis of heart failure with [[mildly reduced ejection fraction]]===
-*The diagnosis of [[HFmrEF]] requires the presence of [[symptoms]] and/or [[signs]] of [[HF]], and a mildly reduced [[EF]] (41-49%) The presence of elevated NPs ([[BNP]] >_35 pg/mL or [[NT-proBNP]] >_125 pg/mL) and other evidence of [[structural heart disease]] including increased [[left atrial]] ([[LA]]) size, [[LVH]] or [[echocardiographic]] measures of [[LV filling]].
+*The diagnosis of [[HFmrEF]] requires the presence of [[symptoms]] and/or [[signs]] of [[HF]], and a mildly reduced [[EF]] (41-49%) The presence of elevated NPs ([[BNP]] ≥35 pg/mL or [[NT-proBNP]] ≥125 pg/mL) and other evidence of [[structural heart disease]] including increased [[left atrial]] ([[LA]]) size, [[LVH]] or [[echocardiographic]] measures of [[LV filling]].<ref name="pmid28370829">{{cite journal |vauthors=Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, Abe R, Oikawa T, Kasahara S, Sato M, Shiroto T, Takahashi J, Miyata S, Shimokawa H |title=Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study |journal=Eur J Heart Fail |volume=19 |issue=10 |pages=1258–1269 |date=October 2017 |pmid=28370829 |doi=10.1002/ejhf.807 |url=}}</ref>
 ===Clinical characteristics ===
 *[[Clinical]] characteristics, [[risk factors]], patterns of [[cardiac remodelling]] are similar to other subgroups of [[HF]].
@@ Line 18: / Line 20: @@
 ===[[Angiotensin receptor II type 1 receptor blockers]]===
-*[[Candesartan]] reduced the number of [[patients]] hospitalized for [[HF]] among those with [[HFmrEF]].
+*[[Candesartan]] reduced the number of [[patients]] hospitalized for [[HF]] among those with [[HFmrEF]].<ref name="pmid13678871">{{cite journal |vauthors=Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J |title=Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial |journal=Lancet |volume=362 |issue=9386 |pages=777–81 |date=September 2003 |pmid=13678871 |doi=10.1016/S0140-6736(03)14285-7 |url=}}</ref>
 *Treatment with [[ARBs]] may be considered in [[patients]] with [[HFmrEF]] [[patients]] with other [[cardiovascular]] indications.
 ===[[Beta-blockers]]===
-* Treatment with [[beta-blockers]] may be considered in [[patients]] with [[HFmrEF]] and another [[cardiovascular]] indication, such as [[AF]] or [[angina]].
+* Treatment with [[beta-blockers]] may be considered in [[patients]] with [[HFmrEF]] and another [[cardiovascular]] indications, such as [[AF]] or [[angina]].<ref name="pmid15642700">{{cite journal |vauthors=Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA |title=Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS) |journal=Eur Heart J |volume=26 |issue=3 |pages=215–25 |date=February 2005 |pmid=15642700 |doi=10.1093/eurheartj/ehi115 |url=}}</ref>
 ===[[ Mineralocorticoid receptor antagonists]]===
-* In a retrospective analysis of the [[TOPCAT]] trial in [[patients]] with  [[LVEF]] >_45%, [[spironolactone]] reduced hospitalizations for [[HF]] in [[patients]] with an [[LVEF]] <55%.
+* In a retrospective analysis of the [[TOPCAT]] trial in [[patients]] with  [[LVEF]] ≥45%, [[spironolactone]] reduced hospitalizations for [[HF]] in [[patients]] with an [[LVEF]] <55%.
 * Treatment with an [[MRA]] may be considered in [[patients]] with [[HFmrEF]].
 ===[[Angiotensin receptor-neprilysin inhibitor]]===
 *Analysis of the [[PARADIGM-HF]] and [[PARAGON-HF]] trials showed that [[sacubitril/valsartan]], compared to other forms of [[RAAS]] blockade reduced [[hospitalizations]] in [[patients]] with [[HFmrEF]].
@@ Line 34: / Line 39: @@
 *There is insufficient evidence regarding  [[CRT]] or [[ICD]] therapy in [[patients]] with [[HFmrEF]].
-===Medications indicated in [[patients]] with [[New York Heart Association]] ([[NYHA]] class II–IV) [[HFmrEF]] ([[heart failure]] with mildly reduced [[ejection fraction]]) ([[LVEF]]41-49%)===
-{| style="cellpadding=0; cellspacing= 0; width: 600px;"
+====Medications indicated in [[patients]] with [[New York Heart Association]] ([[NYHA]] class II–IV) [[HFmrEF]] ([[heart failure]] with mildly reduced [[ejection fraction]]) ([[LVEF]]41-49%)====
+{| style="cellpadding=0; cellspacing= 0; width: 800px;"
 |-
 | style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Recommedation for patients with NYHA class 2-4 heart failure with mildly reduced ejection fraction
@@ Line 58: / Line 68: @@
 |}<ref name="pmid34447992">{{cite journal |vauthors=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A |title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure |journal=Eur Heart J |volume=42 |issue=36 |pages=3599–3726 |date=September 2021 |pmid=34447992 |doi=10.1093/eurheartj/ehab368 |url=}}</ref>
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In [[patients]] with [[HFmrEF]], [[SGLT2i]] can be beneficial in decreasing [[HF]] [[hospitalizations]] and [[cardiovascular]] [[mortality]]. <ref name="pmid34449189">{{cite journal| author=Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M | display-authors=etal| title=Empagliflozin in Heart Failure with a Preserved Ejection Fraction. | journal=N Engl J Med | year= 2021 | volume= 385 | issue= 16 | pages= 1451-1461 | pmid=34449189 | doi=10.1056/NEJMoa2107038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34449189  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=34978853 Review in: Ann Intern Med. 2022 Jan;175(1):JC4] </ref>   ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>
+|}
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Among [[patients]] with current or previous [[symptomatic]] [[HFmrEF]] ([[LVEF]], 41%-49%), use of evidence-based [[beta blockers]] for [[HFrEF]], [[ARNi]], [[ACEi]], or [[ARB]], and [[MRA]]s may be considered to reduce the risk of [[HF]] [[hospitalization]] and [[cardiovascular]] [[mortality]], particularly among [[patients]] with [[LVEF]] on the lower end of this spectrum. <ref name="pmid29040525">{{cite journal| author=Cleland JGF, Bunting KV, Flather MD, Altman DG, Holmes J, Coats AJS | display-authors=etal| title=Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. | journal=Eur Heart J | year= 2018 | volume= 39 | issue= 1 | pages= 26-35 | pmid=29040525 | doi=10.1093/eurheartj/ehx564 | pmc=5837435 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29040525  }} </ref><ref name="pmid31475794">{{cite journal| author=Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP | display-authors=etal| title=Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 17 | pages= 1609-1620 | pmid=31475794 | doi=10.1056/NEJMoa1908655 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31475794  }} </ref><ref name="pmid30429050">{{cite journal| author=Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S | display-authors=etal| title=Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. | journal=Lancet | year= 2019 | volume= 393 | issue= 10166 | pages= 61-73 | pmid=30429050 | doi=10.1016/S0140-6736(18)32484-X | pmc=6319251 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30429050  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=30884498 Review in: Ann Intern Med. 2019 Mar 19;170(6):JC28] </ref><ref name="pmid29096886">{{cite journal| author=Nilsson BB, Lunde P, Grøgaard HK, Holm I| title=Long-Term Results of High-Intensity Exercise-Based Cardiac Rehabilitation in Revascularized Patients for Symptomatic Coronary Artery Disease. | journal=Am J Cardiol | year= 2018 | volume= 121 | issue= 1 | pages= 21-26 | pmid=29096886 | doi=10.1016/j.amjcard.2017.09.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29096886  }} </ref><ref name="pmid26915374">{{cite journal| author=Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K | display-authors=etal| title=Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial. | journal=Circ Heart Fail | year= 2016 | volume= 9 | issue= 3 | pages= e002744 | pmid=26915374 | doi=10.1161/CIRCHEARTFAILURE.115.002744 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26915374  }} </ref><ref name="pmid28370829">{{cite journal| author=Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T | display-authors=etal| title=Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study. | journal=Eur J Heart Fail | year= 2017 | volume= 19 | issue= 10 | pages= 1258-1269 | pmid=28370829 | doi=10.1002/ejhf.807 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28370829  }} </ref><ref name="pmid31736342">{{cite journal| author=Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K | display-authors=etal| title=Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. | journal=Circulation | year= 2020 | volume= 141 | issue= 5 | pages= 352-361 | pmid=31736342 | doi=10.1161/CIRCULATIONAHA.119.044586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31736342  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=32539517 Review in: Ann Intern Med. 2020 Jun 16;172(12):JC65] </ref><ref name="pmid28780577">{{cite journal| author=Zheng SL, Chan FT, Nabeebaccus AA, Shah AM, McDonagh T, Okonko DO | display-authors=etal| title=Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis. | journal=Heart | year= 2018 | volume= 104 | issue= 5 | pages= 407-415 | pmid=28780577 | doi=10.1136/heartjnl-2017-311652 | pmc=5861385 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28780577  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=29255858 Review in: Ann Intern Med. 2017 Dec 19;167(12):JC68] </ref>   ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-NR]])'' <nowiki>"</nowiki>
+|}
+{|
+! colspan="2" style="background: PapayaWhip;" align="center" + |The above table adopted from 2022 AHA Guideline
+|-
+|}<ref name="pmid35363500">{{cite journal| author=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM | display-authors=etal| title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. | journal=Circulation | year= 2022 | volume= 145 | issue= 18 | pages= e876-e894 | pmid=35363500 | doi=10.1161/CIR.0000000000001062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35363500  }} </ref>
+==[[Heart failure]] With Improved [[Ejection Fraction]] ([[HFimpEF]])==
+*[[Medications]] can cause improvement in [[symptoms]], [[functional capacity]], [[LVEF]], and [[reverse remodeling]] in [[patients]] with [[HFrEF]].
+* However, in most [[patients]], [[LV function]] and structural abnormalities do not normalize completely, and [[symptoms]] and [[biomarker]] abnormalities may persist or reoccur.
+* Relapse may occur after withdrawal of [[medication]] despite the period of recovery from [[heart failure]] [[symptoms]] and improvement in [[LVEF]]. Therefore, maintaining the [[medications]] is necessary.
+*In an open-label [[RCT]], discontinuation of [[HF]] medications in known cases of [[dilated cardiomyopathy]]—who were now [[asymptomatic]], improved [[LVEF]]  from <40% to ≥50%, normal [[left ventricular end-diastolic volume]] ([[LVEDV]]), [[NT-proBNP]] concentration <250 ng/L— caused in relapse of [[cardiomyopathy]] and [[HF]] in 40% of the [[patients]] within 6 months.<ref name="pmid30429050">{{cite journal |vauthors=Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu JN, Pantazis A, Cook SA, Ware JS, Baksi AJ, Pennell DJ, Rosen SD, Cowie MR, Cleland JGF, Prasad SK |title=Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial |journal=Lancet |volume=393 |issue=10166 |pages=61–73 |date=January 2019 |pmid=30429050 |pmc=6319251 |doi=10.1016/S0140-6736(18)32484-X |url=}}</ref>
+*  Definition of relapse (at least 1 of these):
+* A reduction in [[LVEF]] by >10% and <50%
+* An increase in [[LVEDV]] by >10% and to higher than the normal range
+* A 2-fold rise in [[NT-proBNP]] concentration and to >400 ng/L
+* Clinical evidence of [[HF]].
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LightGreen"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
+|-
+|bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In [[patients]] with [[HFimpEF]] after [[treatment]], medical therapy should be continued to prevent relapse of [[HF]] and [[LV dysfunction]], even in [[patients]] who may become [[asymptomatic]]. <ref name="pmid30429050">{{cite journal| author=Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S | display-authors=etal| title=Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. | journal=Lancet | year= 2019 | volume= 393 | issue= 10166 | pages= 61-73 | pmid=30429050 | doi=10.1016/S0140-6736(18)32484-X | pmc=6319251 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30429050  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=30884498 Review in: Ann Intern Med. 2019 Mar 19;170(6):JC28] </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>
+|}
+{|
+! colspan="2" style="background: PapayaWhip;" align="center" + |The above tables adopted from 2022 AHA Guideline
+|-
+|}<ref name="pmid35363500">{{cite journal| author=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM | display-authors=etal| title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. | journal=Circulation | year= 2022 | volume= 145 | issue= 18 | pages= e876-e894 | pmid=35363500 | doi=10.1161/CIR.0000000000001062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35363500  }} </ref>
 ==[[Heart failure preserved ejection fraction]] ([[HFpEF]])==
@@ Line 63: / Line 121: @@
 ===Clinical characteristics===
 * [[HFpEF]] [[patients]] are [[older]] and more often [[female]].
-* [[AF]], [[CKD]], and non-[[cardiovascular]] comorbidities are more common in [[patients]] with [[HFpEF]].
+* [[Atrial fibrillation]] ([[AF]]), [[chronic kidney disease]] ([[CKD]]), and non-[[cardiovascular]] comorbidities are more common in [[patients]] with [[HFpEF]].<ref name="pmid32231333">{{cite journal |vauthors=Borlaug BA |title=Evaluation and management of heart failure with preserved ejection fraction |journal=Nat Rev Cardiol |volume=17 |issue=9 |pages=559–573 |date=September 2020 |pmid=32231333 |doi=10.1038/s41569-020-0363-2 |url=}}</ref>
 * It is important to exclude other [[conditions]] that might mimic the [[HFpEF]] syndrome including [[lung]] disease, [[anaemia]], [[obesity]], and [[deconditioning]].
-== The diagnosis of [[heart failure preserved ejection fraction]]==
-*: Echocardiographic criteria:
+=== The diagnosis of [[heart failure preserved ejection fraction]]===
+*: [[Echocardiographic]] criteria:
 *[[ LA]] size ([[LA]] volume index >32 mL/m2)
 * [[Mitral]] E velocity <90 cm/s
@@ Line 73: / Line 132: @@
 *: The diagnosis is made when there are the following:
 (1) [[Symptoms]] and signs of [[HF]]<br>
-(2) An [[LVEF]] >_50%<br>
+(2) An [[LVEF]] ≥ 50%<br>
-(3) Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of [[LV diastolic dysfunction]]/ raised [[LV filling pressures]], including raised [[NPs]]<br>
+(3) Evidence of [[cardiac]] structural and/or functional abnormalities consistent with the presence of [[LV diastolic dysfunction]]/ raised [[LV filling pressures]], including raised [[NPs]]<br>
-*Of note, patients with a history of overtly reduced LVEF (<_40%),
-who later present with LVEF >_50%, should be considered to have
+*In the presence of [[AF]], the threshold for [[LA]] volume index is >40 mL/m2
-recovered HFrEF or ‘HF with improved LVEF’ (rather than HFpEF).
+* [[Exercise stress]] thresholds include E/e' ratio at peak stress ≥ 15 or [[tricuspid regurgitation]] ([[TR]]) velocity at peak stress >3.4 m/s
-Continued treatment for HFrEF is recommended in these patients.271
+* [[LV]] global longitudinal strain <16%
-It is not known whether starting HF therapy in patients with recov�ered LVEF is beneficial. Patients with HFpEF tend to have stable tra�jectory of LVEF over time.272 However, in those who develop a
-clinical indication for a repeat echo during follow-up, around one
+*An invasively measured [[pulmonary capillary wedge pressure]] ([[PCWP]]) of ≥15 mmHg (at rest) or ≥25 mmHg (with exercise) or [[LV end-diastolic pressure ]]≥16 mmHg (at rest) is generally considered diagnostic.<ref name="pmid31472035">{{cite journal |vauthors=Barandiarán Aizpurua A, Sanders-van Wijk S, Brunner-La Rocca HP, Henkens M, Heymans S, Beussink-Nelson L, Shah SJ, van Empel VPM |title=Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction |journal=Eur J Heart Fail |volume=22 |issue=3 |pages=413–421 |date=March 2020 |pmid=31472035 |doi=10.1002/ejhf.1614 |url=}}</ref>
-third have a decline in LVEF.273
+*In the presence of non-invasive markers of raised [[LV filling pressures]], the probability of a diagnosis of [[HFpEF]] increases.<ref name="pmid31132875">{{cite journal |vauthors=Ho JE, Zern EK, Wooster L, Bailey CS, Cunningham T, Eisman AS, Hardin KM, Zampierollo GA, Jarolim P, Pappagianopoulos PP, Malhotra R, Nayor M, Lewis GD |title=Differential Clinical Profiles, Exercise Responses, and Outcomes Associated With Existing HFpEF Definitions |journal=Circulation |volume=140 |issue=5 |pages=353–365 |date=July 2019 |pmid=31132875 |doi=10.1161/CIRCULATIONAHA.118.039136 |url=}}</ref>
-In the presence of AF, the threshold for LA volume index is >40
+* No treatment has been shown to reduce [[mortality]] and [[morbidity]] in [[patients]] with [[HFpEF]].
-mL/m2
+*Hospitalizations for [[HF]] were reduced by [[candesartan]] and [[spironolactone]], [[sacubitril/valsartan]].
-. Exercise stress thresholds include E/e0 ratio at peak
+* Many of [[HFpEF]] [[patients]] have underlying [[hypertension]] and/or [[CAD]], treated with [[ACE-I]]/[[ARB]], [[beta-blockers]], or [[MRAs]].
-stress >_15 or tricuspid regurgitation (TR) velocity at peak stress
+* The [[Food and Drug Administration]] ([[FDA]]) has confirmed the use of [[sacubitril/valsartan]] and [[spironolactone ]] in those with an [[LVEF]] ‘less than normal’.
->3.4 m/s.275 LV global longitudinal strain <16% has a sensitivity of
+* These statements relate to [[patients]] within both the [[HFmrEF]] and [[HFpEF]] categories.
-% and a specificity of 56% for the diagnosis of HFpEF by invasive
+*For sacubitril/valsartan,  subgroup analysis from the [[PARAGON-HF]] study showed a reduction in [[HF]] hospitalizations in [[patients]] with [[LVEF]] <57%, and a meta-analysis of the [[PARADIGM-HF]] and [[PARAGON-HF]] studies showed a reduction in [[cardiovascular]] death and [[HF]] hospitalization in [[patients]] with [[ LVEF]] below the normal range.
-testing.261
+* Use of  [[spironolactone]], in [[TOPCAT]] study was associated with reduced [[cardiovascular]] death and [[HF]] [[hospitalization]],
-The approach to the diagnosis should involve additional confirma�tory tests in cases of diagnostic uncertainty, such as cardiopulmonary
+*Treatment should be aimed at reducing [[symptoms]] of [[congestion]] with [[diuretics]] such as [[loop diuretic]].
-exercise testing (to confirm a reduction in exercise capacity and to
+* [[Thiazide]] [[diuretics]] may be useful for managing [[hypertension]].
-help differentiate the cause of dyspnoea), exercise stress testing, and
+* Reducing [[body weight]] in [[obese]] [[patients]] and increasing [[exercise]] may further improve symptoms and [[exercise capacity]].
-invasive haemodynamic testing.259
+* Notably in [[patients]] with [[HFpEF]], treatment of underlying risk factors, [[etiology]], and coexisting [[comorbidities]] such as [[hypertension]], [[CAD]], [[AF]], [[valvular heart disease]] are recommended.
-If resting echocardiographic and laboratory markers are equivocal,
-a diastolic stress test is recommended.259,274 The confirmatory test
-for the diagnosis of HFpEF is invasive haemodynamic exercise testing.
+{{familytree/start |summary=Sample 8}}{{familytree/start |summary=PE diagnosis Algorithm.}}
-An invasively measured pulmonary capillary wedge pressure
+{{familytree/start}}
-(PCWP) of >_15 mmHg (at rest) or >_25 mmHg (with exercise) or LV
+{{familytree | | | | | | | | | | | | | | A01 | | |A01=[[Diuretic]] as needed
-end-diastolic pressure >_16 mmHg (at rest) is generally considered
+(class1)}}
-diagnostic.266 However, instead of an exercise PCWP cut-off, some
+{{familytree | | | | | | | | | | B01 |-|.|!| | | | | | | | | | |B01=[[SGLT2i]]
-have used an index of PCWP to cardiac output for the invasive diag�nosis of HFpEF260,276. Recognizing that invasive haemodynamic exer�cise testing is not available in many centres worldwide, and is
+(class 2a)|}}
-associated with risks, its main use is limited to the research setting. In
+{{familytree | | | | | | C01 |-|-|-|-|-| C02 | | | | | | | | | |C01=[[MRA]]
-the absence of any disease-modifying treatments, the current guide�lines do not mandate gold standard testing in every patient to make
+(class 2b)|C02=Symptomatic [[heart failure]] with [[LVEF]] ≥ 50%|}}
-the diagnosis, but emphasize that the greater the number of objective
+{{familytree | | | | | | | | | | D01 |-|'| |`|-| D02 | | | | | | | |D01=[[ARNi]]
-non-invasive markers of raised LV filling pressures (Table 9), the
+(class 2b)|D02=[[ARB]]
-higher the probability of a diagnosis of HFpEF.
+class 2b}}
-.4 Treatment of heart failure with
+{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | |}}
-preserved ejection fraction
+{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
-To date, no treatment has been shown to convincingly reduce
+{{familytree/end}}
-mortality and morbidity in patients with HFpEF, although improve�ments have been seen for some specific phenotypes of patients
+{|
-within the overall HFpEF umbrella. However, none of the large
+! colspan="2" style="background: PapayaWhip;" align="center" + |The above tables adopted from 2022 AHA Guideline
-RCTs conducted in HFpEF have achieved their primary endpoints.
+|-
-These include PEP-CHF (perindopril),277 CHARM-Preserved (can�desartan),245 I-PRESERVE (irbesartan),278 TOPCAT (spironolac�tone),246 DIG-Preserved (digoxin),279 and PARAGON-HF
+|}<ref name="pmid35363500">{{cite journal| author=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM | display-authors=etal| title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. | journal=Circulation | year= 2022 | volume= 145 | issue= 18 | pages= e876-e894 | pmid=35363500 | doi=10.1161/CIR.0000000000001062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35363500  }} </ref>
-(sacubitril/valsartan)13 (see Supplementary Table 12 for the details
-about these and additional trials). Hospitalizations for HF were
-reduced by candesartan and spironolactone and there was a trend
-towards reduction with sacubitril/valsartan, although as these trials
-were neutral for their primary endpoints, these are hypothesis�generating findings only. Although nebivolol significantly reduced
-the combined primary endpoint of all-cause mortality or CV hospi�tal admission in the SENIORS trial, this trial included only 15% with
-an LVEF >50%.119,249 Trials targeting the nitric oxide-cyclic guano�sine monophosphate pathway have also failed to improve exercise
-Table 9 Objective evidence of cardiac structural, functional and serological abnormalities ccapacity or QOL in HFpEF, e.g. NEAT-HFpEF,280 INDIE-HFpEF,281
-VITALITY-HFpEF,282 and CAPACITY-HFpEF (praliciguat).283
-Despite the lack of evidence for specific disease-modifying thera�pies in HFpEF, as the vast majority of HFpEF patients have underlying
-hypertension and/or CAD, many are already treated with ACE-I/
-ARB, beta-blockers, or MRAs. In the PARAGON-HF study at base�line, more than 86% of patients were on ACE-I/ARBs, 80% were on
-beta-blockers, and more than 24% were on MRAs.13
-The Task Force acknowledge that the treatment options for
-HFpEF are being revised as this guideline is being published. We note
-that the Food and Drug Administration (FDA) has endorsed the use
-of sacubitril/valsartan and spironolactone in those with an LVEF ‘less
-than normal’. These statements relate to patients within both the
-HFmrEF and HFpEF categories. For sacubitril/valsartan, this decision
-was based on the subgroup analysis from the PARAGON-HF study,
-which showed a reduction in HF hospitalizations in those with an
-LVEF <57%, and a meta-analysis of the PARADIGM-HF and
-PARAGON-HF studies, showing a reduction in CV death and HF
-hospitalization in those with an LVEF below the normal range.247
-Regarding spironolactone, the subgroup of individuals in the
-TOPCAT study recruited in the Americas had a significant reduc�tion in the primary endpoint of CV death and HF hospitalization,
-and a subsequent post hoc analysis by EF showed a significant
-reduction in outcomes for those with an LVEF <55%.9,247 There are
-also ongoing trials with SGLT2 inhibitors. These developments may
-well accelerate a redefinition of HFpEF in the future and have thera�peutic implications.
-In the absence of recommendations regarding disease-modifying
-therapies, treatment should be aimed at reducing symptoms of con�gestion with diuretics. Loop diuretics are preferred, although thiazide
-diuretics may be useful for managing hypertension. Reducing body
-weight in obese patients and increasing exercise may further improve
-symptoms and exercise capacity and should therefore be considered
-in appropriate patients.284,285
-It is important to identify and treat the underlying risk factors, aeti�ology, and coexisting comorbidities in HFpEF (e.g. hypertension in
-section 12.4, CAD in section 12.2, amyloidosis in section 14.6, AF in
-section 12.1.1, and valvular heart disease in section 12.3).
-Undoubtably, treatment of some of the underlying phenotypes of the
-the HFpEF syndrome leads to improVE OUTCOME
-{| style="cellpadding=0; cellspacing= 0; width: 600px;"
+{| style="cellpadding=0; cellspacing= 0; width: 1100px;"
 |-
 | style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Recommedation for treatment of patients with [[HFpEF]] (heart failure preserved ejection fraction)
@@ Line 163: / Line 187: @@
 |-
 |style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
-❑  Screening, treatment, investigation about underlying etiologies, and
+❑  Screening, treatment, investigation of underlying etiologies, and
 [[cardiovascular]] and non-[[cardiovascular]] comorbidities is recommended in [[patients]] with [[HFpEF]]<br>
 ❑[[Diuretics]] are recommended in congested [[patients]] with [[HFpEF]] to improve [[symptoms]] and [[signs]] <br>
@@ Line 172: / Line 196: @@
 |}<ref name="pmid34447992">{{cite journal |vauthors=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A |title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure |journal=Eur Heart J |volume=42 |issue=36 |pages=3599–3726 |date=September 2021 |pmid=34447992 |doi=10.1093/eurheartj/ehab368 |url=}}</ref>
-==Medications==
-===[[Congestive heart failure aldosterone antagonists|Aldosterone Antagonists]]===
-May lead to improvement in [[diastolic]] function and [[hypertrophy]] but not in clinical outcomes.<ref name="pmid23443441">{{cite journal |vauthors=Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, Duvinage A, Stahrenberg R, Durstewitz K, Löffler M, Düngen HD, Tschöpe C, Herrmann-Lingen C, Halle M, Hasenfuss G, Gelbrich G, Pieske B |title=Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial |journal=JAMA |volume=309 |issue=8 |pages=781–91 |year=2013 |pmid=23443441 |doi=10.1001/jama.2013.905 |url=}}</ref><ref name="pmid24716680">{{cite journal |vauthors=Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM |title=Spironolactone for heart failure with preserved ejection fraction |journal=N. Engl. J. Med. |volume=370 |issue=15 |pages=1383–92 |year=2014 |pmid=24716680 |doi=10.1056/NEJMoa1313731 |url=}}</ref> However, a subgroup analysis of patients in the TOPCAT trial with [[brain natriuretic peptide]] levels showed benefit<ref name="pmid24716680" />.
-===[[Congestive heart failure diuretics|Diuretics]]===
-Diuretics are useful to control volume overload and decrease the [[Preload (cardiology)|preload]].<ref name="pmid24720916">{{cite journal |vauthors=Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JG, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O'Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, Gheorghiade M |title=Developing therapies for heart failure with preserved ejection fraction: current state and future directions |journal=JACC Heart Fail |volume=2 |issue=2 |pages=97–112 |year=2014 |pmid=24720916 |pmc=4028447 |doi=10.1016/j.jchf.2013.10.006 |url=}}</ref>
-===[[Congestive heart failure angiotensin receptor-neprilysin inhibitor|Angiotensin receptor neprilysin inhibitors]]===
-They may improve [[symptoms]] and quality of life in HFpEF patients but clinical trials to evaluate their effectiveness are ongoing.<ref name="pmid26386501">{{cite journal |vauthors=Macdonald PS |title=Combined angiotensin receptor/neprilysin inhibitors: a review of the new paradigm in the management of chronic heart failure |journal=Clin Ther |volume=37 |issue=10 |pages=2199–205 |year=2015 |pmid=26386501 |doi=10.1016/j.clinthera.2015.08.013 |url=}}</ref><ref name="pmid26976916">{{cite journal |vauthors=Hubers SA, Brown NJ |title=Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition |journal=Circulation |volume=133 |issue=11 |pages=1115–24 |year=2016 |pmid=26976916 |doi=10.1161/CIRCULATIONAHA.115.018622 |url=}}</ref><ref name="pmid27324636">{{cite journal |vauthors=Prenner SB, Shah SJ, Yancy CW |title=Role of Angiotensin Receptor-Neprilysin Inhibition in Heart Failure |journal=Curr Atheroscler Rep |volume=18 |issue=8 |pages=48 |year=2016 |pmid=27324636 |doi=10.1007/s11883-016-0603-4 |url=}}</ref>
-===[[Congestive heart failure ACE inhibitors|ACE inhibitors]]===
-[[ACE inhibitor|ACE inhibitors]] do not have direct effect on mortality and morbidity in HFpEF but they have great role on [[hypertension]], renal function, [[Coronary heart disease|CAD]] and [[Diabetes mellitus|diabetes]] as underlying disease.<ref name="pmid18208835">{{cite journal |vauthors=Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, Yip T, Lau ST, Lau CP, Tang MO, Yu CM, Sanderson JE |title=The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction |journal=Heart |volume=94 |issue=5 |pages=573–80 |year=2008 |pmid=18208835 |doi=10.1136/hrt.2007.117978 |url=}}</ref><ref name="pmid13678871">{{cite journal |vauthors=Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J |title=Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial |journal=Lancet |volume=362 |issue=9386 |pages=777–81 |year=2003 |pmid=13678871 |doi=10.1016/S0140-6736(03)14285-7 |url=}}</ref>
-===[[Congestive heart failure angiotensin receptor blockers|Angiotensin II receptor blockers]]===
+{|class="wikitable" style="width:80%"
-There is no evidence that they improve [[morbidity]] or [[mortality]] in HFpEF patients.<ref name="pmid13678871">{{cite journal |vauthors=Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J |title=Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial |journal=Lancet |volume=362 |issue=9386 |pages=777–81 |year=2003 |pmid=13678871 |doi=10.1016/S0140-6736(03)14285-7 |url=}}</ref>
+|-
+| colspan="1" style="text-align:center; background:LightGreen"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
+|-
+|bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[Patients]] with [[HFpEF]] and [[hypertension]] should have [[medication]] titrated to attain [[blood pressure]] targets in accordance with published [[clinical practice guidelines]] to prevent [[morbidity]]. <ref name="pmid27454050">{{cite journal| author=Thomopoulos C, Parati G, Zanchetti A| title=Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials. | journal=J Hypertens | year= 2016 | volume= 34 | issue= 10 | pages= 1921-32 | pmid=27454050 | doi=10.1097/HJH.0000000000001052 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27454050  }} </ref><ref name="pmid27195814">{{cite journal| author=Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM | display-authors=etal| title=Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial. | journal=JAMA | year= 2016 | volume= 315 | issue= 24 | pages= 2673-82 | pmid=27195814 | doi=10.1001/jama.2016.7050 | pmc=4988796 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27195814  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=27538175 Review in: Ann Intern Med. 2016 Aug 16;165(4):JC14]  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=27872159 Review in: Evid Based Med. 2017 Mar;22(1):30] </ref><ref name="pmid26551272">{{cite journal| author=SPRINT Research Group. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM | display-authors=etal| title=A Randomized Trial of Intensive versus Standard Blood-Pressure Control. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 22 | pages= 2103-16 | pmid=26551272 | doi=10.1056/NEJMoa1511939 | pmc=4689591 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26551272  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=26882300 Review in: Ann Intern Med. 2016 Feb 16;164(4):JC15]  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=27008978 Review in: Evid Based Med. 2016 Jun;21(3):101] </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C-LD]])'' <nowiki>"</nowiki>
+|}
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In [[patients]] with [[HFpEF]], [[SGLT2i]] can be beneficial in decreasing [[HF]] [[hospitalizations]] and [[cardiovascular]] [[mortality]]. <ref name="pmid34449189">{{cite journal| author=Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M | display-authors=etal| title=Empagliflozin in Heart Failure with a Preserved Ejection Fraction. | journal=N Engl J Med | year= 2021 | volume= 385 | issue= 16 | pages= 1451-1461 | pmid=34449189 | doi=10.1056/NEJMoa2107038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34449189  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=34978853 Review in: Ann Intern Med. 2022 Jan;175(1):JC4] </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:B-R]])'' <nowiki>"</nowiki>
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In [[patients]] with [[HFpEF]], [[management]] of [[AF]] can be useful to improve [[symptoms]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C-EO]])'' <nowiki>"</nowiki>
+|}
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' In selected [[patients]] with [[HFpEF]], [[MRA]]s may be considered to decrease [[hospitalizations]], particularly among [[patients]] with [[LVEF]] on the lower end of this spectrum. <ref name="pmid24716680">{{cite journal| author=Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B | display-authors=etal| title=Spironolactone for heart failure with preserved ejection fraction. | journal=N Engl J Med | year= 2014 | volume= 370 | issue= 15 | pages= 1383-92 | pmid=24716680 | doi=10.1056/NEJMoa1313731 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24716680  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25329223 Review in: Ann Intern Med. 2014 Oct 21;161(8):JC6] </ref><ref name="pmid25406305">{{cite journal| author=Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N | display-authors=etal| title=Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. | journal=Circulation | year= 2015 | volume= 131 | issue= 1 | pages= 34-42 | pmid=25406305 | doi=10.1161/CIRCULATIONAHA.114.013255 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25406305  }} </ref><ref name="pmid26915374">{{cite journal| author=Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K | display-authors=etal| title=Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial. | journal=Circ Heart Fail | year= 2016 | volume= 9 | issue= 3 | pages= e002744 | pmid=26915374 | doi=10.1161/CIRCHEARTFAILURE.115.002744 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26915374  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:B-R]])'' <nowiki>"</nowiki>
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''5.''' In selected [[patients]] with [[HFpEF]], the use of [[ARB]] may be considered to decrease [[hospitalizations]], particularly among [[patients]] with [[LVEF]] on the lower end of this spectrum. <ref name="pmid13678871">{{cite journal| author=Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ | display-authors=etal| title=Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. | journal=Lancet | year= 2003 | volume= 362 | issue= 9386 | pages= 777-81 | pmid=13678871 | doi=10.1016/S0140-6736(03)14285-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13678871  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=15122853 Review in: ACP J Club. 2004 Mar-Apr;140(2):32-3] </ref><ref name="pmid29431256">{{cite journal| author=Lund LH, Claggett B, Liu J, Lam CS, Jhund PS, Rosano GM | display-authors=etal| title=Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. | journal=Eur J Heart Fail | year= 2018 | volume= 20 | issue= 8 | pages= 1230-1239 | pmid=29431256 | doi=10.1002/ejhf.1149 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29431256  }} </ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>
+|-
+|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''6.''' In selected [[patients]] with [[HFpEF]], [[ARNi]] may be considered to decrease [[hospitalizations]], particularly among [[patients]] with [[LVEF]] on the lower end of this spectrum. <ref name="pmid31475794">{{cite journal| author=Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP | display-authors=etal| title=Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 17 | pages= 1609-1620 | pmid=31475794 | doi=10.1056/NEJMoa1908655 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31475794  }} </ref><ref name="pmid31736342">{{cite journal| author=Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K | display-authors=etal| title=Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. | journal=Circulation | year= 2020 | volume= 141 | issue= 5 | pages= 352-361 | pmid=31736342 | doi=10.1161/CIRCULATIONAHA.119.044586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31736342  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=32539517 Review in: Ann Intern Med. 2020 Jun 16;172(12):JC65] </ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>
+|}
+{|class="wikitable" style="width:80%"
+|-
+| colspan="1" style="text-align:center; background:LightCoral"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
+|-
+|bgcolor="LightCoral"|<nowiki>"</nowiki>'''7.''' In [[patients]] with [[HFpEF]], routine use of [[nitrates]] or [[phosphodiesterase-5 inhibitors]] to increase activity or [[QOL]] is ineffective. <ref name="pmid26549714">{{cite journal| author=Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH | display-authors=etal| title=Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 24 | pages= 2314-24 | pmid=26549714 | doi=10.1056/NEJMoa1510774 | pmc=4712067 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26549714  }} </ref><ref name="pmid23478662">{{cite journal| author=Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G | display-authors=etal| title=Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. | journal=JAMA | year= 2013 | volume= 309 | issue= 12 | pages= 1268-77 | pmid=23478662 | doi=10.1001/jama.2013.2024 | pmc=3835156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23478662  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:B-R]])'' <nowiki>"</nowiki>
+|}
+{|
+! colspan="2" style="background: PapayaWhip;" align="center" + |The above tables adopted from 2022 AHA Guideline
+|-
+|}<ref name="pmid35363500">{{cite journal| author=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM | display-authors=etal| title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. | journal=Circulation | year= 2022 | volume= 145 | issue= 18 | pages= e876-e894 | pmid=35363500 | doi=10.1161/CIR.0000000000001062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35363500  }} </ref>
-===[[Congestive heart failure beta blockers|β-blockers]]===
+==External Link==
-[[Beta blockers|β-blockers]] have not shown benefits in HFpEF.<ref name="pmid22983988">{{cite journal |vauthors=Yamamoto K, Origasa H, Hori M |title=Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF) |journal=Eur. J. Heart Fail. |volume=15 |issue=1 |pages=110–8 |year=2013 |pmid=22983988 |doi=10.1093/eurjhf/hfs141 |url=}}</ref><ref name="pmid22147202">{{cite journal |vauthors=Conraads VM, Metra M, Kamp O, De Keulenaer GW, Pieske B, Zamorano J, Vardas PE, Böhm M, Dei Cas L |title=Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study |journal=Eur. J. Heart Fail. |volume=14 |issue=2 |pages=219–25 |year=2012 |pmid=22147202 |doi=10.1093/eurjhf/hfr161 |url=}}</ref>
+*[https://www.ahajournals.org/doi/epub/10.1161/CIR.0000000000001063.full.pdf 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines]<ref name="pmid35363499">{{cite journal |vauthors=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW |title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines |journal=Circulation |volume=145 |issue=18 |pages=e895–e1032 |date=May 2022 |pmid=35363499 |doi=10.1161/CIR.0000000000001063 |url=}} </ref>
 ==References==

Congestive heart failure with preserved EF pharmacotherapy: Difference between revisions

Latest revision as of 15:31, 19 August 2022

Overview

Heart failure mildly reduced ejection fraction (HPmrEF), EF (41-49%)

The diagnosis of heart failure with mildly reduced ejection fraction

Clinical characteristics

Treatment

Angiotensin-converting enzyme inhibitors

Angiotensin receptor II type 1 receptor blockers

Beta-blockers

Mineralocorticoid receptor antagonists

Angiotensin receptor-neprilysin inhibitor

Other drugs

Devices

Medications indicated in patients with New York Heart Association (NYHA class II–IV) HFmrEF (heart failure with mildly reduced ejection fraction) (LVEF41-49%)

Heart failure With Improved Ejection Fraction (HFimpEF)

Heart failure preserved ejection fraction (HFpEF)

Clinical characteristics

The diagnosis of heart failure preserved ejection fraction

External Link

References

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