Approach
Goals of treatment of HFpEF are to:
Alleviate symptoms
Improve cardiac function, functional capacity, and quality of life
Reduce hospitalisations
Management of HFpEF is focused on reducing congestion, identification and treatment of underlying causes and comorbidities, implementing lifestyle disease-modifying therapy, and measures where appropriate (exercise, diet, weight control).[2][3][4][5]
The following recommendations cover ongoing management of HFpEF. For details of management of acute exacerbation of heart failure, see Acute heart failure.
For details of management of HFpEF mimics, see separate topics.
Lifestyle measures
Lifestyle changes, dietary and nutritional modifications, exercise training, and health maintenance have the potential to reduce heart failure (HF) progression.[77] Weight loss should be promoted in patients who are overweight.
Exercise training or regular physical activity is recommended to improve function and quality of life.[3][78][79][80][81] Cardiac rehabilitation, which includes medical evaluation, education on adherence to medication, advice on diet, psychosocial support, and an exercise training and physical activity programme can also be recommended to improve function, exercise tolerance, and quality of life. US guidelines advise that patients who are on optimal guideline-directed medical treatment for HF, in stable medical condition, and able to participate in an exercise programme are candidates for an exercise rehabilitation programme.[3] There is developing evidence to support home-based cardiac rehabilitation alternatives to centre-based programmes.[82][83][84]
Dietary sodium intake is an easily modifiable factor. There is limited evidence for sodium restriction in patients with heart failure; however, guidelines recommend that excessive sodium intake should be avoided.[3][4][85][86] Tobacco and alcohol discontinuation should be encouraged.
Treatment of underlying causes and comorbidities
Screen for and manage underlying causes and comorbidities of HFpEF, such as hypertension, ischaemic heart disease, dyslipidaemia, atrial fibrillation, diabetes, chronic kidney disease (CKD), obesity, and sleep apnoea.[2][5] Consult your local drug information source for details of cautions, contraindications, and dose adjustments that may be required in the presence of comorbid conditions.
See 'Considerations for management of specific comorbidities' section below for more information on management of HFpEF with specific comorbidities.
Pharmacotherapy
Sodium-glucose cotransporter-2 (SGLT2) inhibitors
SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) are recommended for patients with HFpEF to decrease heart failure hospitalisations and cardiovascular mortality.[2][3][5][87][88]
The EMPEROR-Preserved trial found that empagliflozin reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with HFpEF, regardless of the presence or absence of diabetes, and across the spectrum of baseline kidney function compared with placebo.[89][90][91][92] Effects were sustained for 1-3 years of treatment and reversed after withdrawal.[93] Patients who received empagliflozin also had an early and sustained reduction in risk and severity of a broad range of inpatient and outpatient events, such as a decrease in the need for hospitalisations requiring aggressive therapy, a decrease of worsening events requiring intensification of diuretics, and an increased likelihood of functional class improvement.[94] Health-related quality of life was also improved.[95] The effects were similar in women and men, and seen across a broad age spectrum.[96][97] The effects were also similar regardless of background diuretic use and empagliflozin was also associated with a reduced likelihood of diuretic initiation or dose escalation and an increased likelihood of diuretic de-escalation and discontinuation after randomisation.[98]
The PRESERVED-HF trial compared dapagliflozin with placebo in patients with HFpEF and found that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations, and exercise function, and was well tolerated in chronic HFpEF.[99][100] The DELIVER trial found that dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction, both in those with and without history of recent heart failure hospitalisation, across the spectrum of baseline kidney function and glycaemic range, and regardless of the duration of heart failure.[101][102][103][104][105][106][107][108][109][110] The effects were also similar regardless of background diuretic use and dapagliflozin was also associated with a reduced likelihood of diuretic initiation.[111] Overall health status, as reported by KCCQ, was improved with dapagliflozin.[112][113] Improvements in symptoms, physical function, and quality of life were larger in patients with the greatest level of frailty.[114] The efficacy and safety of dapagliflozin was also found to be consistent across the spectrum of BMI, with a larger absolute effect seen in patients with obesity.[115] In a pooled analysis of the DELIVER (patients with HFpEF) and DAPA-HF (patients with HFrEF) trials, the response to dapagliflozin was similar between men and women across the range of ejection fraction.[116]
Meta-analyses have shown that SGLT2 inhibitors reduce the risk of cardiovascular death and hospitalisations for heart failure in a broad range of patients with heart failure.[117][118][119][120] In one meta-analysis of 15 randomised trials involving 20,241 patients with heart failure, SGLT2 inhibitors significantly reduced all-cause and cardiovascular mortality compared with placebo, and the composite of cardiovascular mortality or hospitalisations/urgent visits for heart failure was reduced with SGLT2 inhibitors across subgroups of sex, age, race, estimated glomerular filtration rate (eGFR), functional class, and ejection fraction.[118] Another meta-analysis found that in HFpEF and HFmrEF, SGLT2 inhibitors, angiotensin receptor-neprilysin inhibitors, and aldosterone antagonists were associated with a significant decrease in the risk of heart failure hospitalisation compared with placebo, with SGLT2 inhibitors the optimal drug class in terms of reducing the risk for heart failure hospitalisation.[121] Combining data from three randomised controlled trials (PRESERVED-HF, DEFINE-HF [Dapagliflozin effect on symptoms and biomarkers in patients with heart failure], and CHIEF-HF [A study on impact of canagliflozin on health status, quality of life, and functional status in heart failure] found that treatment with an SGLT2i resulted in health status improvements for both black and white patients with heart failure.[122]
Diuretics
All patients with signs of congestion should receive diuretics to relieve symptoms and prevent worsening heart failure.[2][3][4][5]
Loop diuretics used for the treatment of heart failure and congestion include furosemide, bumetanide, and torsemide. The most commonly used agent appears to be furosemide, but some patients may respond more favourably to another loop diuretic. In treatment resistance, loop diuretics should be combined with a thiazide diuretic (e.g., chlorothiazide, hydrochlorothiazide) or a thiazide-like diuretic (e.g., metolazone, indapamide).
Careful monitoring of renal function and electrolytes is essential. The minimum dose of diuretic should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight. Some patients may be able to come off the diuretics completely, but they need very close long-term follow-up.
Aldosterone antagonists
US guidelines recommend that aldosterone antagonists (e.g., spironolactone, eplerenone) should be considered in patients with HFpEF with and without congestion particularly among those with lower LVEF.[2][3] For patients with HFpEF and congestion, an aldosterone antagonist can be started upfront with or without loop diuretics.[11]
European guidelines make no recommendation for aldosterone antagonists in HFpEF.
One Cochrane review found that aldosterone antagonists in HFpEF have a modest beneficial effect in reducing heart failure hospitalisation, but they probably have little or no effect on cardiovascular mortality and quality of life.[123]
The TOPCAT trial compared spironolactone with placebo in patients with HFpEF (EF 45% or more) and found no significant difference in the primary end point, a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalisation for heart failure.[124] The trial included participants in the US, Canada, Brazil, Argentina, Russia, and Georgia. Post-hoc analysis suggested that there were clinical benefits with spironolactone in patients with HFpEF from the Americas, with a significant reduction in the primary end point. In Russia and Georgia, all clinical event rates were markedly lower, and there was no detectable impact of spironolactone on any outcomes.[125] Further post-hoc analysis by ejection fraction showed the potential efficacy of spironolactone was greatest at the lower end of the LVEF spectrum.[126]
Spironolactone and eplerenone can both cause hyperkalaemia, and precautions should be taken to minimise the risk; regular monitoring of serum potassium and renal function is recommended.[3]
Angiotensin receptor-neprilysin inhibitor (ARNi)
US guidelines recommend that sacubitril/valsartan may be considered for selected patients with HFpEF, particularly among those with lower LVEF.[2][3]
European guidelines make no recommendation for sacubitril/valsartan in HFpEF.
One Cochrane review found that ARNi treatment in HFpEF has a modest beneficial effect in reducing heart failure hospitalisation, but probably has little or no effect on cardiovascular mortality and quality of life.[123]
The PARAGON-HF trial compared sacubitril/valsartan with valsartan alone in patients with HFpEF (EF 45% or more) and found that sacubitril/valsartan did not achieve a significant reduction in the primary composite end point of cardiovascular death or total (first and recurrent) heart failure hospitalisations.[127] In pre-specified subgroup analyses, sacubitril/valsartan was shown to be beneficial in reducing hospitalisation patients at the lower end of the LVEF spectrum (defined as a median EF of ≤57%) and in women.[127][128]
The PARALLAX trial compared sacubitril/valsartan with standard medical therapy (enalapril, valsartan, or placebo) in patients with HFpEF (EF 40% or more) and found sacubitril/valsartan significantly decreased plasma NT-pro-BNP concentration at 12 weeks, but did not improve submaximal exercise capacity.[129]
Angiotensin-II receptor antagonists
US guidelines recommend that angiotensin-II receptor antagonists may be considered for selected patients with HFpEF, particularly among those with lower LVEF.[2][3]
European guidelines make no recommendation for angiotensin-II receptor antagonists in HFpEF.
One Cochrane review found there was no evidence supporting an important beneficial effect of angiotensin-II receptor antagonists on mortality and hospitalisation outcomes in patients with HFpEF and that their use in HFpEF in the absence of an alternative indication is not supported.[123]
In the CHARM-preserved trial, candesartan was compared with placebo in patients with HFpEF (EF 40% or more) but there was no significant difference in the primary end point of cardiovascular death or heart failure hospitalisation between the two groups.[130] Post-hoc analysis showed the potential efficacy of candesartan was greatest at the lower end of the LVEF spectrum.[126]
Considerations for management of specific comorbidities
Hypertension
Treatment of HFpEF is similar in patients with and without hypertension.[4] Thiazide diuretics may be preferred over loop diuretics in those with HF, hypertension and mild fluid retention as they confer more persistent antihypertensive effects.[3]
The recommended target systolic BP in those with HFpEF is <130 mmHg.[2] When considering antihypertensive therapy in patients with HFpEF, beta-blockers are generally avoided as negative chronotropic effects may reduce tolerability.[2]
Atrial fibrillation (AF)
AF and HF may cause or exacerbate each other and the relationship is complex. HF therapies should be optimised. Treatment of AF involves correction of the abnormal rate/rhythm, along with anticoagulation. Options for rate and rhythm control are determined by the presence of HF and extent of LV dysfunction.[3][4]
Obesity
Pharmacotherapy with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to improve patient-oriented quality of life outcomes (measured by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [KCCQ-CSS] and 6-minute walk distance at 52 weeks) in patients with obesity and HFpEF and results in greater weight loss compared with placebo.[83] In semaglutide-treated patients, the improvements in quality of life outcomes were greater with larger body weight reduction.[84]
Surgically induced weight loss in individuals with class III obesity (body mass index [BMI] 40 or above) has been shown to reverse left ventricular (LV) hypertrophy and restore diastolic function.[52][131]
See Obesity in adults.
Diabetes
Treatment of HFpEF is similar in patients with and without diabetes. SGLT2 inhibitors are recommended as first-line treatment of hyperglycaemia in patients with type 2 diabetes and HF to reduce HF-related morbidity and mortality.[3][4] See also information above on SGLT2 inhibitors.
Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is recommended for the prevention of HF hospitalisation in patients with CKD and type 2 diabetes.[2][5]
See Overview of diabetes.
Chronic coronary disease
Patients with HFpEF and suggestive symptoms should be assessed for presence of coronary artery disease (CAD).[2]
Revascularisation in those with HFpEF and CAD has been associated with less deterioration of LV function and improved outcomes; however, prospective trials are needed to determine optimal treatment of these patients.[2]
Sleep disorders
Patients with HF and daytime sleepiness may have sleep studies to assess for obstructive sleep apnoea and central sleep apnoea.[3][4]
In patients with HF and obstructive sleep apnoea, continuous positive airway pressure is recommended to improve sleep quality and reduce daytime sleepiness, however it does not seem to reduce mortality.[3][4]
See Obstructive sleep apnoea, and Central sleep apnoea.
Chronic kidney disease
The effectiveness of guideline-directed medical therapy (GDMT) for HF in patients with concomitant CKD is uncertain.[132] Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source for more information.
Most patients will tolerate mild-to-moderate degrees of functional renal impairment without difficulty. Initiation of GDMT for HF with a SGLT2 inhibitor, ARNi, or angiotensin-II receptor antagonist may result in an initial rise in serum creatinine and a drop in eGFR, but this change is generally transient and should not be a reason for discontinuation.[2][4]
An increase in serum creatinine of <50% above baseline, up to 3 mg/dL, or a decrease in eGFR of <10% from baseline, as long as eGFR is >25 mL/min/1.73 m², may be considered as acceptable.
If the serum creatinine increases to >3 mg/dL, the renal insufficiency can severely limit the efficacy and enhance the toxicity of established treatments.[133][134]
Aldosterone antagonists should be used with caution in patients with CKD and hyperkalaemia. The US guidelines advise that they are only initiated in patients with eGFR >30mL/min/1.73m² and serum potassium <5.0 mEq/L.[3]
Consultation with a nephrology consultant should be considered.
Hyperlipidaemia
All patients with HFpEF and hyperlipidaemia will need lifestyle modifications and most will also require treatment with a statin possibly with additional non-statin lipid-lowering therapy.
For details of management of HF with hypercholesterolaemia, see Hypercholesterolaemia (Management approach).
Thyroid disorders
Both hypo- and hyperthyroidism are associated with HF and assessment of thyroid function is recommended.
Thyroid disorders are treated as per endocrinology guidelines; referral to endocrinologist should be considered.
Depression
Depression is common in patients with HF and is associated with a reduced quality of life and increased mortality. Treatment with conventional therapies (e.g., antidepressants) does not seem to directly improve these outcomes. However, interventions that focus on improving HF self-care (e.g., psychotherapy, selective serotonin-reuptake inhibitors [SSRIs], or nurse-led support) may reduce hospitalisation and mortality in patients with moderate or severe depression.[3][4]
See Depression in adults.
Cancer
Patients who develop HF secondary to cancer therapy should be treated with GDMT. Generally, GDMT should not be discontinued unless there are specific and compelling reasons to hold these medicines and this should be managed by a multidisciplinary team. Before starting any cardiotoxic cancer therapy baseline cardiac function should be measured and ongoing monitoring after completion of a course of chemotherapy may be helpful for risk stratification.[3][4]
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