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]

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.

• 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, 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.

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

• 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.

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

• 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.

• 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.

• 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.

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

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• 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.

• 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.

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