Heart Failure with Reduced Versus Preserved Ejection Fraction: A Comprehensive Review on Morbidity, Mortality, Patient Characteristics and Therapeutic Outcomes

Aluri Venkata Rama Krishna Sai Charan, Chetana Lalasa Singamsetty, Kavya Vakicharla, Jyothika Yerranagu, Dr. M. Bhargavi, Dr. Y. Prapurna Chandra,

doi:10.5281/zenodo.18723601

Review Paper | Open Access
Volume 04 | Issue 02 | Article Id IJPS/260402287

Heart Failure with Reduced Versus Preserved Ejection Fraction: A Comprehensive Review on Morbidity, Mortality, Patient Characteristics and Therapeutic Outcomes
Aluri Venkata Rama Krishna Sai Charan* Chetana Lalasa Singamsetty Kavya Vakicharla Jyothika Yerranagu Dr. M. Bhargavi Dr. Y. Prapurna Chandra
Ratnam Institute of Pharmacy, Nellore, Andhra Pradesh.

Abstract

Heart failure (HF) is a progressive and multifactorial clinical syndrome that reminds as a leading cause of morbidity, mortality and healthcare worldwide. Heart failure is broadly categorized into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) based on left ventricular ejection fraction (LVEF). These two phenotypes shares clinical features but differs in underlying mechanisms, patient characteristics, outcomes, therapeutic response. While HFrEF has been associated with poor survival, recent improvements in guideline directed medical therapy have altered its clinical trajectory. In contrast HFpEF has emerged as an increasingly prevalent phenotype, and particularly among elderly patients with multiple comorbidities and continuous to pose diagnostic and therapeutic challenges. This review includes the literatures published between 2019 to 2025 to provide a comparative evaluation of morbidity, mortality, patient profiles and therapeutic outcomes in both the phenotypes. The data indicates that patients with HFpEF experience morbidity comparative or greater than those with HFrEF, largely driven by current hospitalizations and systemic comorbid conditions. Although mortality remains higher in HFrEF, emerging evidence suggests a narrowing mortality gap between two phenotypes due to improved HFrEF survival and increasing recognization of non-cardiovascular mortality in HFpEF. Therapeutic advances have established this is modifying HFrEF, whereas management of HFpEF remains largely centered on controlling the symptoms and comorbidity management. This review highlights critical differences and overlaps between HFpEF and HFrEF and underscores the need for phenotype specific strategies to optimize patient outcomes in healthcare.

Keywords

Heart Failure, HFrEF, HFpEF, Ejection fraction, Morbidity, Mortality

Introduction

The cardiovascular system is a complex , dynamic in the way that it achieves its basic function which is to transport blood throughout the body. cardiovascular system consists of heart , which is a multifaceted that is not only center for pumping aspects but also as secondary endocrine gland.

1. THE HEART

Heart is a muscular vital organ that functions as the central pump of the circulatory system, ensuring the continuous flow of blood throughout body. Heart is protected by the rib cage and rests on the diaphragm, enclosed within double-layered sac called the pericardium, which reduces friction during its rhythmic contractions. Structurally, heart consist of 4 chambers that are right atrium and right ventricle, which handle deoxygenated blood returning from body. the left atrium and left ventricle, which manage oxygen-rich blood from lungs. The right atrium receives blood from superior and inferior vena cava, passing it to right ventricle, which pumps it to lungs via pulmonary artery. Oxygenated blood then enters left atrium through pulmonary veins, moves into left ventricle and is forcefully pumped into the aorta to supply the entire body. To maintain one-way circulation, the heart contains four valves: the tricuspid, pulmonary, mitral, and aortic valves. Its wall is composed of three layers—the endocardium, myocardium, and epicardium—each serving a specific role in protection and contraction. Working tirelessly, heart beat records around 100,000 times daily, delivering oxygen and nutrients while removing waste products, making it indispensable for sustaining life¹.

2. HEART FAILURE

Heart failure a common cardiovascular disorder which is characterized by heart inability to deliver adequate cardiac output to meet systemic metabolic demands or as a consequence of reduced cardiac pump function². Despite advances in cardiovascular medicine, it is associated with more hospitalization rates, impaired life quality and premature death worldwide. Heart failure a heterogeneous syndrome that is classified according to left ventricular ejection fraction (LVEF) into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)².

2.1 CLASSIFICATION:

Heart failure is classified on the bases of left ventricular function of heart, that the disfunction or abnormalities of left ventricle represents the type of heart failure.

Table1: Classification Of Heart Failure.

Feature	Heart Failure with Reduced Ejection Fraction	Heart Failure With Preserved Ejection Fraction	Heart Failure with Mid-Range Ejection Fraction	Heart Failure with Improved Ejection Fraction
LV EF	≤ 40%	≤ 50%	41–49%	Previously ≤40%, now >40%
Primary problem	Systolic dysfunction (poor contraction)	Diastolic dysfunction (poor relaxation/ filling)	Mixed systolic + diastolic	Recovery of systolic function
LV size	Dilated	Normal or concentric hypertrophy	Variable	Often improved from prior dilation
Common causes	Ischemic heart disease, MI, dilated cardiomyopathy	Hypertension, aging, obesity, diabetes, AF	Same as HFrEF/HFpEF overlap	GDMT response, revascularization, reverse remodeling
Typical patients	Younger, more often male	Older, more often female	Intermediate characteristics	characteristics Prior HFrEF patients

Heart Failure is classified based on left ventricular ejection fraction (LVEF) of heart into :

(Normal EF (55–70%) shows that heart is functioning well)
Reduced EF (<40%) is a hallmark of systolic heart failure.
Preserved EF (≥50%) can still be associated with HF symptoms due to impaired filling (diastolic dysfunction).
Borderline EF (50–55%) may require monitoring, as it can progress toward dysfunction.
High EF (>70%) is not always healthy and may reflect abnormal heart muscle thickening.

The left ventricular ejection fraction is measured by 2D Echo or echocardiography³.

2.2 STAGES OF HEART FAILURE³:

Heart failure is classified into four progressive stages (A–D) by the American Heart Association and American College of Cardiology. Stage A means risk without structural disease, while Stage D represents advanced heart failure with severe symptoms.

Stage A – At Risk

Individuals are at risk developing HF but not have structural heart disease or symptoms. Common factors that increases the risk includes hypertension, diabetes, obesity, and family history. The focus here is on prevention by changing lifestyle and medical management of underlying conditions.

Risk factors in this stage include:

Hypertension
Coronary artery disease
Diabetes Mellitus
Cardiotoxic agents
Cardiomyopathy Genetic variants
History of cardiomyopathy in family.

Stage B – Structural Changes Without Symptoms

At this stage, it represents structural heart disease, such as previous heart damage, valve disease, or reduced ejection fraction, but patients do not show symptoms. Early treatment with medications like ACE inhibitors or beta-blockers is often recommended to slow progression.

Stage C – Symptomatic Heart Failure

Patients have heart disease structurally along with current or past symptoms such as breathlessness, fatigue, or swelling. This is the stage where heart failure becomes clinically evident.

Stage D – Advanced Heart Failure

This is the severe stage, where symptoms persist even at rest despite optimal treatment. Patients often require advanced therapies such as heart transplant, mechanical support devices, or palliative care.

Figure 1 : Overview Of Heart Failure.

2.3 EPIDEMIOLOGY :

Heart failure has subjected to intrest since it was designated as a new epidemic in 1997. HF has been firstly described as emerging epidemic but at present because of ageing population the HF patients still continues to rise. However, the heart failure cases are evolving although frequency of cases has steadied and also reducing in some populations⁴.

The incidence relatively observed in young, possibly increase in obesity. Similarly the evidence shows that patients with HF may be on risk in developing countries that struggling from communicable diseases associated with a western type lifestyle⁴.

2.4 GLOBAL BURDEN:

Heart failure is associated with considerable morbidity and mortality, along with reduced physical capacity, diminished life quality and substantial healthcare costs. Globally, more than 64 million individuals are affected. The prevalence of HF among adults is estimated to be between 1% and 3%. People aged over 70 years account for approximately 62.2% of all cases. In older age groups, women show a higher prevalence, whereas men are more commonly affected at younger ages. Although women represent about half of the population with HF, the age?standardized prevalence is greater among men.

2.5 PATIENT CHARECTERSTICS :

HEART FAILURE WITH REDUCED EJECTION FRACTION:

Patients are typically younger, predominantly male, and often have a history of myocardial infarction, ischemic heart disease, or dilated cardiomyopathy. Additional risk factors are smoking, alcohol use, and genetic cardiomyopathies. Structural changes such as left ventricular dilation and eccentric hypertrophy are common^7-8.

HEART FAILURE WITH PRESERVED EJECTION FRACTION :

Patients are usually older and more likely to be female. Hypertension is most prevalent risk factor, frequently accompanied by obesity, T₂DM, atrial fibrillation, CKD, and anemia¹¹. HFpEF is increasingly recognized as a systemic syndrome rather than a purely cardiac disorder, with significant involvement of vascular, renal, pulmonary, and skeletal muscle systems⁹.

Table 2: comparative data of patient characteristics between HFrEF and HFpEF.

Characteristic	HFrEF	HFpEF
Typical age group	Middle-aged to elderly	Elderly
Gender predominance	Male	Female
Aetiology	Ischemic heart disease, cardiomyopathy	Hypertension, metabolic syndrome
Ventricular function	Reduced systolic function	Preserved systolic, impaired diastolic
Comorbidity burden	Moderate	High
Atrial fibrillation prevalence	Moderate	High

2.6 RISK FACTORS:

Risk factors and lifestyle habits that can increase your chance of HF. Most people suffers with heart failure may have any other heart condition first¹⁰.

Having one or more of these risk factors highly increases risk of HF :

Coronary Artery Disease (CAD)
Hypertension
T₂DM
Metabolic Syndrome
Thyroid Problems
Aging
Smoking
Obesity
Alcohol or Drug Abuse
Certain Radiation and Chemotherapy

Table 3:Risk Factors For Heart Failure^3,10

Risk Factor	What it is / Mechanism	How it Contributes to Heart Failure (Key Points)
Coronary Artery Disease (CAD)	Cholesterol and fatty deposits narrow coronary arteries (atherosclerosis), reducing blood supply to heart muscle.	Causes angina; complete blockage can lead to myocardial infarction (heart attack). CAD can also contribute to hypertension, and long-term high BP can lead to HF.
High Blood Pressure (Hypertension)	Increased pressure in blood vessels forces the heart to pump harder.	Long-term workload causes cardiac remodeling, chamber enlargement, and weakening → leads to HF.
Type 2 Diabetes Mellitus	Diabetes promotes insulin resistance, endothelial dysfunction, and accelerated atherosclerosis.	Increases HF risk independently and is often associated with hypertension and dyslipidemia. Raises risk for both HFrEF and HFpEF.
Metabolic Syndrome	Cluster of metabolic abnormalities (≥3 risk factors).	Defined by ≥3 of: abdominal obesity, high triglycerides, low HDL, high BP, and high fasting glucose. These metabolic factors increase HF development risk.
Thyroid Problems	Thyroid hormones affect heart rate, contractility and fluid balance.	Hyperthyroidism: persistent tachycardia and thickening heart muscle. Hypothyroidism: bradycardia, fluid retention, and diastolic dysfunction.
Aging	Age-related stiffening and weakening of heart muscle.	Risk increases significantly after 65 years; older adults are more likely to develop HF.
Smoking	Promotes vascular damage and atherosclerosis.	Increases HF risk by worsening CAD and contributing to hypertension and vascular disease.
Obesity / Overweight	Increases cardiac workload and metabolic burden.	Strongly linked with hypertension, diabetes, dyslipidemia, and structural cardiac changes → increases HF risk.
Alcohol or Drug Abuse	Causes direct toxic effects on the myocardium and may affect rhythm.	Can weaken heart muscle and lead to cardiomyopathy → increases HF risk.
Certain Radiation and Chemotherapy	Some therapies cause cardiotoxic effects.	May damage heart muscle, reduce cardiac function, and increase HF risk.

2.7 PATHOPHYSIOLOGY:

Pathophysiology of HFrEF²¹:

Risk factors like ischemic Heart disease, Mi, Cardiomyopathy, Myocarditis

↓

Myocardial injury.

↓

Loss of functional cardiomyocytes.

↓

Reduced myocardial contractility.

↓

Reduced stroke volume and cardiac output.

↓

Activation of compensatory mechanisms.

↓

Increase heart rate, vasoconstriction, retention of sodium and water.

↓

Increased preload and afterload.

↓

Adverse ventricular remodelling like lv dilation, wall thinning, fibrosis.

↓

Progressive systolic dysfunction.

↓

Clinical manifestations like dyspnea, fatigue, edema that leads to complications such as arrhythmias, sudden cardiac death, pump function.

Pathophysiology of HFpEF²¹:

Risk factors such as aging, hypertension, obesity, diabetes, CKD, AF.

↓

Chronic systemic inflammation.

↓

Endothelial dysfunction.

↓

Coronary microvascular dysfunction.

↓

Myocardial fibrosis and increased ventricular stiffness.

↓

Impaired ventricular relaxation (diastolic dysfunction).

↓

Increased left ventricular filling pressure.

↓

Pulmonary congestion during exertion.

↓

Preserved systolic function (normal ejection fraction).

↓

Exercise intolerance and HF symptoms like dyspnea, fatigue.

↓

Frequent decompensation triggered by comorbidities.

2.8 CLINICAL PRESENTATION AND DIAGNOSIS

While HFrEF and HFpEF share a common clinical presentation marked by fatigue, peripheral edema, orthopnea, and dyspnea upon exertion their diagnostic pathways require combination of biomarker analysis, imaging, and physical examination.

Echocardiography remains the primary diagnostic tool for evaluating LVEF, heart chamber size, and diastolic performance. Additionally, natriuretic peptides serve as vital markers for both diagnosis and prognosis. However, it is important to note that peptide concentrations may be comparatively lower in HFpEF cases, often due to the influence of obesity or the presence of concentric remodeling^22-24.

2.9 MORBIDITY PATTERNS

In HF, morbidity is characterized by diminished functional capacity, a lower life quality, and frequent readmissions to the hospital¹⁷. Patients with HFpEF often face higher rates of hospitalization than those with HFrEF, a trend primarily attributed to the presence of non-cardiac comorbidities. Conversely, morbidity in HFrEF is more directly linked to the progression of pump failure, the occurrence of arrhythmias, and risk of sudden cardiac death^26-27.

Table 4: comparison of morbidity patterns in HFrEF VS HFpEF.

Parameter	HFrEF	HFpEF
Hospitalization frequency	High	Very high
Primary cause of admission	Pump failure, arrhythmias	Comorbidities, overload of volume
Excess intolerance	Severe	Moderate to severe
Quality of life impairment	Significant	Significant
Length of hospital stay	Moderate	Often prolonged
Readmission	High	Very high

1. MORTALITY OUTCOMES

Historically, heart failure with reduced ejection fraction was linked to a higher rate of cardiovascular mortality compared to heart failure with preserved ejection fraction²⁸. Nevertheless, contemporary data indicate an upward trend in survival rates for patients with reduced ejection fraction, alongside a growing awareness of non-cardiovascular deaths within this group²⁹. Conversely, individuals with HFpEF exhibit a higher likelihood of succumbing to non-cardiac conditions, including stroke, infections, and renal failure³⁰.

Table 5: mortality characteristics in HFrEF VS HFpEF.

Aspect	HFrEF	HFpEF
Overall mortality	High	Moderate to high
Cardiovascular mortality	Predominant	Lower
Non cardiovascular mortality	Lower	High
Sudden cardiac death	Common	Less common
cases over last decade	Declining	Relatively unchanged

2.11 THERAPEUTIC MANAGEMENT

HEART FAILURE WITH REDUCED EJECTION FRACTION:

Clinical guidelines for managing HFrEF now advocate for a "four-pillar" foundational strategy. This approach—consisting of beta-blockers, mineralocorticoid receptor antagonists (MRAs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and angiotensin receptor-neprilysin inhibitors (ARNIs)—has been shown to markedly decrease both mortality rates and hospital admissions^31-34.

ARNIs: Specifically sacubitril/valsartan, these agents offer superior protection against cardiovascular death and hospitalization compared to traditional ACE inhibitors. They work through a dual mechanism: suppressing the renin-angiotensin-aldosterone system while simultaneously boosting natriuretic peptide levels³⁵.
BETA-BLOCKERS: Evidence-based options like bisoprolol, carvedilol, and metoprolol succinate enhance survival by mitigating chronic sympathetic overactivity and halting the progression of negative ventricular remodeling³⁶.
MRAs: Medications such as eplerenone and spironolactone contribute to lower morbidity and mortality by utilizing anti-inflammatory and antifibrotic pathways³⁷.
SGLT2 INHIBITORS: Empagliflozin and dapagliflozin have recently become essential components of HFrEF care. These drugs consistently lowers’ risk of death and heart failure-related hospitalization, providing benefits to patients regardless of whether they have diabetes^38.

HEART FAILURE WITH PRESERVED EJECTION FRACTION:

The treatment of HFpEF primarily emphasizes symptom relief, rigorous blood pressure management, and the effective treatment of underlying comorbidities. A significant therapeutic milestone has been reached with recent clinical trials demonstrating that SGLT2 inhibitors effectively lower the risk of hospital admissions⁴⁴.

TRADITIONAL ANTIHYPERTENSIVES: While agents such as ACE inhibitors, ARBs, and MRAs have been shown to decrease hospitalization rates, they have not demonstrated a significant impact on mortality within the HFpEF population ^32-33.
SGLT2 INHIBITOR SUCCESS: Recent evidence has firmly established SGLT2 inhibitors as the first drug class to achieve a substantial reduction in heart failure-related hospitalizations for HFpEF patients, marking a major clinical breakthrough in the field ^34-35.

Shift Toward Patient-Centered Care: Due to high frequency of non-cardiovascular comorbidities and various competing causes of mortality, the clinical approach to HFpEF is shifting. Modern management increasingly prioritizes a patient-centered strategy—addressing the individual’s overall health profile—rather than focusing exclusively on cardiac-specific interventions³⁶.

1. EMERGING THERAPIES AND FUTURE DIRECTIONS

Current research is increasingly prioritizing phenotype-specific treatments, the discovery of novel biomarkers, and the implementation of precision medicine to manage the diverse nature of HFpEF and further refine HFrEF outcomes⁴⁵.

Innovative therapeutic approaches are now targeting previously overlooked pathways that drives progression of heart failure. For HFrEF, new agents such as the cardiac myosin activator like omecamtiv mecarbil are designed to improve heart muscle contractility. Crucially, this is achieved without raising myocardial oxygen demand or intracellular calcium levels, presenting a promising option for treating advanced stages of the disease⁴⁵.

In context of HFpEF, scientific investigation has shifted toward addressing systemic inflammation, myocardial fibrosis, metabolic imbalances, and endothelial impairment⁴⁴. Current clinical studies are exploring several promising avenues, including:

Antifibrotic agents which reduces cardiac stiffness.
Modulators of the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway.
Therapies targeting microvascular dysfunction and the metabolic impact of epicardial adipose tissue²¹.

CONCLUSION

Although they share overlapping clinical features, HFrEF and HFpEF represent distinct heart failure phenotypes with fundamental differences in their epidemiological profiles, underlying pathophysiology, and mortality rates. Their responses to medical interventions also vary significantly. While innovative therapies have revolutionized the prognosis for those with HFrEF, HFpEF continues to be major clinical challenge where many therapeutic needs remain unmet. To effectively manage the increasing global impact of this disease, it is vital to maintain a focus on ongoing research and the development of management strategies tailored to these specific phenotypes.

REFERENCES

Section Three: Chapter 14: Cardiovascular Physiology – The Heart. In: Physiology Text. San Diego Miramar College, 2023: 784; 788–790; 801.
Camm AJ, Lüscher TF and Serruys PW, editors: ESC Textbook of Cardiovascular Medicine. 3rd Edition. Oxford University Press, Oxford, 2018: 836.
Bozkurt B, Coats AJS, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N, Anker SD, Atherton J, Böhm M, Butler J, Drazner MH, Lam CSP, et al.: Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. European Journal of Heart Failure (2021), 23(3):352–380 doi:10.1002/ejhf.2115.
Groenewegen A, Rutten FH, Mosterd A and Hoes AW: Epidemiology of heart failure. European Journal of Heart Failure (2020), 22(8):1342–1356. doi:10.1002/ejhf.1858. PMID: 32483830. PMCID: PMC7540043.
Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC and Coats AJS: Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovascular Research (2023), 118(17):3272–3287. doi:10.1093/cvr/cvac013. PMID:35150240.
Jia Z, Du X, Gao H. Epidemiology and burden of heart failure. Cardiol Discov. 2025;5(4):281–284. doi:10.1097/cd9.0000000000000173.
Schwinger RHG: Pathophysiology of heart failure. Cardiovascular Diagnosis and Therapy (2021), 11(1):263–276.doi:10.21037/cdt-20-302. PMID:33708498; PMCID:PMC7944197.
Murphy SP, Ibrahim NE and Januzzi JL Jr: Heart failure with reduced ejection fraction: a review. Journal of the American Medical Association (2020), 324(5):488–504. doi:10.1001/jama.2020.10262.
Ho JE, Gona P, Pencina MJ, Tu JV, Austin PC, Vasan RS, et al.: Discriminating clinical features of heart failure with preserved vs reduced ejection fraction in the community. European Heart Journal (2012), 33(14):1734–1741. doi:10.1093/eurheartj/ehs070.
Levy D, Larson MG, Vasan RS, Kannel WB and Ho KK: The progression from hypertension to congestive heart failure. Journal of the American Medical Association (1996), 275(20):1557–1562.doi:10.1001/jama.1996.03530440031032.
Ho KK, Pinsky JL, Kannel WB and Levy D: The epidemiology of heart failure: the Framingham Study. Journal of the American College of Cardiology (1993), 22(4 Suppl A):6A–13A. doi:10.1016/0735-1097(93)90520-Z.
Murphy SP, Ibrahim NE and Januzzi JL Jr: Heart failure with reduced ejection fraction: a review. Journal of the American Medical Association (2020), 324(5):488–504. doi:10.1001/jama.2020.10262.
Messerli FH, Rimoldi SF and Bangalore S: The transition from hypertension to heart failure. Journal of the American College of Cardiology (2017), 70(11):1413–1423. doi:10.1016/j.jacc.2017.07.772.
MacDonald MR, Petrie MC, Hawkins NM, et al.: Diabetes, left ventricular systolic dysfunction, and chronic heart failure. European Heart Journal (2008), 29(10):1224–1240. doi:10.1093/eurheartj/ehn156.
Isomaa B, Almgren P, Tuomi T, et al.: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetologia (2001), 44(4):239–244 doi:10.1007/s001250051607.
Wang J, Hu H, Zhang C, et al.: Metabolic syndrome and risk of incident heart failure. International Journal of Cardiology (2023), 379:66–75 doi:10.1016/j.ijcard.2023.03.024.
Biondi B and Kahaly GJ: Thyroid dysfunction and heart failure. European Journal of Endocrinology (2013), 169(5):R167–R179. doi:10.1530/EJE-12-0627.
Rodondi N, Aujesky D, Vittinghoff E, et al.: Subclinical thyroid dysfunction and the risk of heart failure events. Circulation (2010), 121(7):904–911. doi:10.1161/CIRCULATIONAHA.109.096024.
Roger VL: Epidemiology of heart failure. Circulation Research (2021), 128(10):1421–1434. doi:10.1161/CIRCRESAHA.121.318172.
Yusuf S, Hawken S, Ounpuu S, et al.: Effect of potentially modifiable risk factors associated with myocardial infarction. The Lancet (2004), 364(9438):937–952. doi:10.1016/S0140-6736(04)17018-9.
Zipes DP, Libby P, Bonow RO, Mann DL, Tomaselli GF, Braunwald E, editors. Braunwald’s heart disease: a textbook of cardiovascular medicine. 11th ed. Philadelphia (PA): Elsevier; 2019:487–556.
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726. doi:10.1093/eurheartj/ehab368.
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. Circulation. 2022;145(18):e895–e1032. doi:10.1161/CIR.0000000000001063
Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 heart failure guideline. Circulation. 2017;136(6):e137–e161. doi:10.1161/CIR.0000000000000509.
Dunlay SM, Redfield MM, Weston SA, et al. Hospitalizations after heart failure diagnosis: a community perspective. J Am Coll Cardiol. 2009;54(18):1695–1702. doi:10.1016/j.jacc.2009.08.019
Desai AS, Stevenson LW. Rehospitalization for heart failure: predict or prevent? Circulation. 2012;126(4):501–506. doi:10.1161/CIRCULATIONAHA.112.125435
Gheorghiade M, Vaduganathan M, Fonarow GC, Bonow RO. Rehospitalization for heart failure. J Am Coll Cardiol. 2013;61(4):391–403. doi:10.1016/j.jacc.2012.09.038
Solomon SD, Claggett B, Lewis EF, et al. Influence of ejection fraction on cardiovascular outcomes in heart failure. Eur Heart J. 2016;37(5):455–462. doi:10.1093/eurheartj/ehv498
Vaduganathan M, Claggett BL, Jhund PS, et al. Contemporary treatment patterns and outcomes of HFrEF. JAMA Cardiol. 2020;5(10):1144–1153. doi:10.1001/jamacardio.2020.2480.
Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355(3):251–259. doi:10.1056/NEJMoa052256
Greene SJ, Butler J, Fonarow GC. Simultaneous or rapid sequence initiation of foundational therapies for HFrEF. Circulation. 2021;143(9):875–890. doi:10.1161/CIRCULATIONAHA.120.050552.
Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020;17(9):559–573. doi:10.1038/s41569-020-0363-2
Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved ejection fraction. Lancet. 2003;362(9386):777–781. doi:10.1016/S0140-6736(03)14285-7
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with preserved ejection fraction. N Engl J Med. 2021;385(16):1451–1461. doi:10.1056/NEJMoa2107038.
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in HFpEF. N Engl J Med. 2022;387(12):1089–1098. doi:10.1056/NEJMoa2206286.
Borlaug BA. Shift toward patient-centered care in HFpEF. Nat Rev Cardiol. 2020;17:559–573. doi:10.1038/s41569-020-0363-2
McMurray JJV, Packer M, Desai AS, et al. Angiotensin–neprilysin inhibition vs enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004. doi:10.1056/NEJMoa1409077.
Packer M, Anker SD, Butler J, et al. Empagliflozin in HFrEF. N Engl J Med. 2020;383(15):1413–1424. doi:10.1056/NEJMoa2022190.
Zannad F, McMurray JJV, Krum H, et al. Eplerenone in HFrEF. N Engl J Med. 2011;364(1):11–21. doi:10.1056/NEJMoa1009492
Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil. N Engl J Med. 2021;384(2):105–116. doi:10.1056/NEJMoa2025797
Vaduganathan M, Claggett BL, Jhund PS, et al. Non-cardiovascular deaths in HFrEF. JAMA Cardiol. 2020;5(10):1144–1153. doi:10.1001/jamacardio.2020.2480
Owan TE, Hodge DO, Herges RM, et al. Non-cardiac mortality in HFpEF. N Engl J Med. 2006;355(3):251–259. doi:10.1056/NEJMoa052256.
Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors reduce HF hospitalizations in HFpEF. N Engl J Med. 2021;385:1451–1461. doi:10.1056/NEJMoa2107038
Shah SJ, Borlaug BA, Kitzman DW, et al. Precision medicine and emerging therapies in HFpEF. Circulation. 2020;141(12):1001–1026. doi:10.1161/CIRCULATIONAHA.119.041886.
Teerlink JR, Diaz R, Felker GM, et al. Omecamtiv mecarbil in advanced HFrEF. N Engl J Med. 2021;384(2):105–116.