Congestive heart failure with preserved EF pharmacotherapy
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
- 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
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 |
| The above table adopted from 2021 ESC Guideline |
|---|
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.[5]
- 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.[6]
- In the presence of non-invasive markers of raised LV filling pressures, the probability of a diagnosis of HFpEF increases.[7]
- 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.
| 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 |
| The above table adopted from 2021 ESC Guideline |
|---|
References
- ↑ 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.
- ↑ 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) - ↑ 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.