Congestive heart failure Treatment of Heart failure with preserved ejection fraction: Difference between revisions

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__NOTOC__
__NOTOC__
{{Congestive heart failure}}
{{Congestive heart failure}}
{{CMG}};{{AE}}{{MehdiP}}
{{CMG}};{{AE}} {{Sara.Zand}} {{MehdiP}}
==Overview==
==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.
[[Hear failure]] has been divided into three subgroups including [[heart failure reduced EF]], [[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.
==HFpEF pharmacotherapy==
Treatment for HFpEF is based on underlying associated conditions. These measure are mainly focused on:
*[[Hypertension]] Control<ref name="pmid18378519">{{cite journal |vauthors=Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ |title=Treatment of hypertension in patients 80 years of age or older |journal=N. Engl. J. Med. |volume=358 |issue=18 |pages=1887–98 |year=2008 |pmid=18378519 |doi=10.1056/NEJMoa0801369 |url=}}</ref>
:It is recommended to maintain [[BP]] less than 150/90 mm Hg in persons who are 60 years of age or older in the general population and of less than 140/90 mm Hg in persons with [[kidney]] disease (estimated GFR<60 ml per minute per 1.73 m2 of body-surface area or >30 mg of albumin per gram of [[creatinine]],regardless of [[Diabetes mellitus|diabetic]] status) and for persons with [[Diabetes mellitus|diabetes]], regardless of age.<ref name="pmid25114277">{{cite journal |vauthors=Reisin E, Harris RC, Rahman M |title=Commentary on the 2014 BP guidelines from the panel appointed to the Eighth Joint National Committee (JNC 8) |journal=J. Am. Soc. Nephrol. |volume=25 |issue=11 |pages=2419–24 |year=2014 |pmid=25114277 |pmc=4214539 |doi=10.1681/ASN.2014040371 |url=}}</ref>
*Control of volume overload<ref name="pmid25737498">{{cite journal |vauthors=Takei M, Kohsaka S, Shiraishi Y, Goda A, Izumi Y, Yagawa M, Mizuno A, Sawano M, Inohara T, Kohno T, Fukuda K, Yoshikawa T |title=Effect of estimated plasma volume reduction on renal function for acute heart failure differs between patients with preserved and reduced ejection fraction |journal=Circ Heart Fail |volume=8 |issue=3 |pages=527–32 |year=2015 |pmid=25737498 |doi=10.1161/CIRCHEARTFAILURE.114.001734 |url=}}</ref><ref name="pmid21366472">{{cite journal |vauthors=Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM |title=Diuretic strategies in patients with acute decompensated heart failure |journal=N. Engl. J. Med. |volume=364 |issue=9 |pages=797–805 |year=2011 |pmid=21366472 |pmc=3412356 |doi=10.1056/NEJMoa1005419 |url=}}</ref>
:Diuretics must be used to relief symptoms of volume overload according to patients' weight, [[symptoms]] and [[electrolyte]] status. Also, [[sodium]] restriction may be helpful in patients who are prone to volume overload.<ref name="pmid27206819">{{cite journal |vauthors=Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P |title=2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC |journal=Eur. Heart J. |volume=37 |issue=27 |pages=2129–200 |year=2016 |pmid=27206819 |doi=10.1093/eurheartj/ehw128 |url=}}</ref>
*[[Atrial fibrillation]] treatment<ref name="pmid23908348">{{cite journal |vauthors=Zakeri R, Chamberlain AM, Roger VL, Redfield MM |title=Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study |journal=Circulation |volume=128 |issue=10 |pages=1085–93 |year=2013 |pmid=23908348 |pmc=3910441 |doi=10.1161/CIRCULATIONAHA.113.001475 |url=}}</ref>
:Patients with [[Atrial fibrillation]] (AF) must be treated according to last guideline for rate control and anti coagulation but if the [[symptoms]] remained consider rhythm control.<ref name="pmid24682348">{{cite journal |vauthors=January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW |title=2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society |journal=Circulation |volume=130 |issue=23 |pages=2071–104 |year=2014 |pmid=24682348 |doi=10.1161/CIR.0000000000000040 |url=}}</ref>
*Appropriate [[diet]] and [[exercise]]<ref name="pmid21350053">{{cite journal |vauthors=Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, Carson PE |title=Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial |journal=Circ Heart Fail |volume=4 |issue=3 |pages=324–31 |year=2011 |pmid=21350053 |pmc=3100162 |doi=10.1161/CIRCHEARTFAILURE.110.959890 |url=}}</ref><ref name="pmid22536983">{{cite journal |vauthors=Smart NA, Haluska B, Jeffriess L, Leung D |title=Exercise training in heart failure with preserved systolic function: a randomized controlled trial of the effects on cardiac function and functional capacity |journal=Congest Heart Fail |volume=18 |issue=6 |pages=295–301 |year=2012 |pmid=22536983 |doi=10.1111/j.1751-7133.2012.00295.x |url=}}</ref>
*Weight control<ref name="pmid21350053">{{cite journal |vauthors=Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, Carson PE |title=Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial |journal=Circ Heart Fail |volume=4 |issue=3 |pages=324–31 |year=2011 |pmid=21350053 |pmc=3100162 |doi=10.1161/CIRCHEARTFAILURE.110.959890 |url=}}</ref>
*Control of co-morbid conditions, such as [[Diabetes mellitus|diabetes]], [[anemia]], [[hyperlipidemia]], [[sleep apnea]] and [[COPD]].<ref name="pmid26243795">{{cite journal |vauthors=Alehagen U, Benson L, Edner M, Dahlström U, Lund LH |title=Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50 |journal=Circ Heart Fail |volume=8 |issue=5 |pages=862–70 |year=2015 |pmid=26243795 |doi=10.1161/CIRCHEARTFAILURE.115.002143 |url=}}</ref>
*Patients with [[Coronary heart disease|coronary artery diseases]] (CAD) should be treated based on the guidelines recommendations.


==Medications==
== [[Heart failure mildly reduced ejection fraction]] ([[HPmrEF]]), [[EF]] (41-49%) ==
===[[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]]===
===The diagnosis of heart failure with [[mildly reduced ejection fraction]]===
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>
*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>
===[[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]]===
===Clinical characteristics ===
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>
*[[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]].


===[[Congestive heart failure beta blockers|β-blockers]]===
===[[Angiotensin receptor II type 1 receptor blockers]]===
[[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>
*[[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.


== 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure/2013 ACCF/AHA Guideline for the Management of Heart Failure.<ref name="pmid23741057">{{cite journal |vauthors=Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL |title=2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines |journal=Circulation |volume=128 |issue=16 |pages=1810–52 |year=2013 |pmid=23741057 |doi=10.1161/CIR.0b013e31829e8807 |url=}}</ref> (DO NOT EDIT)==
===[[Beta-blockers]]===
{|class="wikitable" style="width:80%"
* 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>
|-
 
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
===[[ 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%.
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Systolic and diastolic blood pressure should be controlled according to published guidelines.<ref name="pmid14656957">{{cite journal |vauthors=Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ |title=Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure |journal=Hypertension |volume=42 |issue=6 |pages=1206–52 |year=2003 |pmid=14656957 |doi=10.1161/01.HYP.0000107251.49515.c2 |url=}}</ref><ref name="pmid8622246">{{cite journal |vauthors=Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK |title=The progression from hypertension to congestive heart failure |journal=JAMA |volume=275 |issue=20 |pages=1557–62 |year=1996 |pmid=8622246 |doi= |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
* Treatment with an [[MRA]] may be considered in [[patients]] with [[HFmrEF]].
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Diuretics should be used for relief of symptoms due to volume overload.''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|}


{|class="wikitable" style="width:80%"
===[[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]].
| colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
=== 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.
| bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or QoL in patients with HFpEF is ineffective.<ref name="pmid23478662">{{cite journal |vauthors=Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E |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 |volume=309 |issue=12 |pages=1268–77 |year=2013 |pmid=23478662 |pmc=3835156 |doi=10.1001/jama.2013.2024 |url=}}</ref><ref name="pmid26549714">{{cite journal |vauthors=Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, LeWinter MM, Joseph SM, Shah SJ, Semigran MJ, Felker GM, Cole RT, Reeves GR, Tedford RJ, Tang WH, McNulty SE, Velazquez EJ, Shah MR, Braunwald E |title=Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction |journal=N. Engl. J. Med. |volume=373 |issue=24 |pages=2314–24 |year=2015 |pmid=26549714 |pmc=4712067 |doi=10.1056/NEJMoa1510774 |url=}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])''<nowiki>"</nowiki>
*Therefore, there are insufficient data to recommend its use.
|-
*There are insufficient data on [[ivabradine]] in [[HFmrEF]].
| bgcolor="LightCoral"|<nowiki>"</nowiki>'''2.''' Routine use of nutritional supplements is not recommended for patients with HFpEF.''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
=== Devices===
|}
*There is insufficient evidence regarding  [[CRT]] or [[ICD]] therapy in [[patients]] with [[HFmrEF]].


{|class="wikitable" style="width:80%"
===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;"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| 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
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite medical therapy ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |''' [[Diuretics]] ([[ESC guidelines classification scheme|Class I, Level of Evidence C]]):'''
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Management of atrial fibrillation according to published guidelines in patients with HFpEF is reasonable to improve symptomatic HF ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑ [[Diuretics]] are recommended in [[patients]] with [[congestion]] and [[HFmrEF]] in order reduce [[symptoms]] and [[signs]]<br>
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' Use of β-blockers, ACE inhibitors, and ARBs for hypertension in patients with HFpEF. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |''' [[ACEI]] ([[ESC guidelines classification scheme|Class IIb, Level of Evidence C]]):'''
|-
|-
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑ [[ACE-I]] may be considered for patients with [[HFmrEF]] to reduce the risk of [[HF]] hospitalization and death<br>
❑ [[ARB]] may be indicated for [[patients]] with [[HFmrEF]] to reduce the risk of [[HF]] hospitalization and death<br>
❑ [[Beta-blocker]] may be considered for [[patients]] with [[HFmrEF]] to reduce the risk of [[HF]] hospitalization and death,<br>
❑ [[MRA]] may be considered for patients with [[HFmrEF]] to reduce the risk of [[HF]] hospitalization and death<br>
❑[[Sacubitril/valsartan]] may be considered for [[patients]] with [[HFmrEF]] to reduce the risk of [[HF]] hospitalization and death<br>
|}
|}
{|class="wikitable" style="width:80%"
{|
! colspan="2" style="background: PapayaWhip;" align="center" + |The above table adopted from 2021 ESC Guideline
|-
|}<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>
 
==[[Heart failure preserved ejection fraction]] ([[HFpEF]])==
*
===Clinical characteristics===
* [[HFpEF]] [[patients]] are [[older]] and more often [[female]].
* [[AF]], [[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:
*[[ 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]]<br>
(2) An [[LVEF]] ≥ 50%<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>
 
*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.<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>
*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>
* 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.
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
| 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)
 
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.'''ARBs might be considered to decrease hospitalizations for patients with HFpEF.<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> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''([[ESC guidelines classification scheme|Class I, Level of Evidence C]]):'''
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.'''In appropriately selected patients with HFpEF (with EF ≥45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists might be considered to decrease hospitalizations.<ref name="pmid25881932">{{cite journal |vauthors=Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY, Mao CT, Lin JF, Ho HY, Yang NI |title=Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics |journal=J. Am. Coll. Cardiol. |volume=65 |issue=15 |pages=1509–20 |year=2015 |pmid=25881932 |doi=10.1016/j.jacc.2015.02.018 |url=}}</ref><ref name="pmid25006730">{{cite journal |vauthors=Morawietz H, Bornstein SR |title=Spironolactone for heart failure with preserved ejection fraction |journal=N. Engl. J. Med. |volume=371 |issue=2 |pages=181 |year=2014 |pmid=25006730 |doi=10.1056/NEJMc1405715#SA4 |url=}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])''<nowiki>"</nowiki>
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑  Screening, treatment, investigation about 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>
|}
|}
{|
! colspan="2" style="background: PapayaWhip;" align="center" + |The above table adopted from 2021 ESC Guideline
|-
|}<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>


==References==
==References==

Latest revision as of 14:12, 2 March 2022

Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure Treatment of Heart failure with preserved ejection fraction On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure Treatment of Heart failure with preserved ejection fraction

CDC on Congestive heart failure Treatment of Heart failure with preserved ejection fraction

Congestive heart failure Treatment of Heart failure with preserved ejection fraction in the news

Blogs on Congestive heart failure Treatment of Heart failure with preserved ejection fraction

Directions to Hospitals Treating Congestive heart failure Treatment of Heart failure with preserved ejection fraction

Risk calculators and risk factors for Congestive heart failure Treatment of Heart failure with preserved ejection fraction

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]

Overview

Hear failure has been divided into three subgroups including heart failure reduced EF, 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

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%)

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]

Heart failure preserved ejection fraction (HFpEF)

Clinical characteristics

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%
Recommedation for treatment of patients with HFpEF (heart failure preserved ejection fraction)
(Class I, Level of Evidence C):

❑ Screening, treatment, investigation about 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]

References

  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. ↑ 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.
  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.
  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)
  5. ↑ 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).
  6. ↑ 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)
  7. ↑ 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.

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