Heart Failure With Reduced Ejection FractionEdit
Heart Failure With Reduced Ejection Fraction is a clinical syndrome arising from impaired systolic function of the left ventricle, typically defined by a left ventricular ejection fraction (LVEF) at or below 40%. It represents a major component of the broader condition known as heart failure, which also includes phenotypes with preserved or mid-range ejection fraction. HFrEF results from diverse causes, with ischemic heart disease, long-standing hypertension, cardiomyopathies, and valvular disease among the most common. Advances in understanding biology and the development of guideline-directed therapies have substantially changed outcomes over the past two decades, reducing both symptoms and the risk of death for many patients.
In clinical terms, HFrEF expresses a failure of the heart’s pumping capacity that leads to insufficient blood flow to meet bodily needs and to elevated pressures in the heart that back up into the lungs or body. Symptoms often include shortness of breath with exertion or at rest, fatigue, swelling of the legs or abdomen, and reduced exercise tolerance. The condition is a major source of hospitalizations and a leading cause of morbidity and mortality in adults.
This article summarizes the medical understanding of HFrEF, from physiology to practical management, and notes the debates that accompany evolving therapies and health care delivery.
Pathophysiology and natural history
The failing heart in HFrEF undergoes a cascade of neurohormonal activation and structural remodeling. Reduced output triggers compensatory mechanisms, notably activation of the renin–angiotensin–aldosterone system (renin–angiotensin–aldosterone signaling) and heightened sympathetic activity. These responses, initially helpful, promote further heart muscle injury, fibrosis, and dilatation, creating a vicious cycle of worsening function and symptoms. Over time, changes in myocardial energy use, calcium handling, and endothelial function contribute to ongoing decline in contractility and vascular regulation.
Left ventricular remodeling and scar formation can create an arrhythmogenic substrate, increasing the risk of sudden cardiac events. Hypertensive and ischemic heart disease pathways, as well as genetic and inflammatory factors, shape the specific pattern of disease in each patient. The trajectory of HFrEF is heterogeneous; some patients experience rapid deterioration, while others stabilize or even improve with appropriate treatment and lifestyle adjustments.
Key components of the pathophysiology include: - cardiomyocyte injury and death with replacement by scar tissue; - maladaptive chamber dilation and wall stress; - persistent neurohormonal drive that perpetuates fluid retention and edema; - endothelial dysfunction and microvascular abnormalities.
For deeper background, see Heart failure and Left ventricular ejection fraction.
Diagnosis and assessment
Diagnosis rests on a combination of symptoms, physical examination, imaging, and biomarkers. Typical manifestations include dyspnea on exertion or at rest, orthopnea, fatigue, edema, and reduced exercise capacity. Physical findings may include elevated jugular venous pressure, displaced apical impulse, crackles in the lungs, and peripheral edema.
Key diagnostic tools: - Imaging: Echocardiography is central to confirming reduced LVEF and to characterizing cardiac structure and function. See echocardiography and Left ventricular ejection fraction. - Biomarkers: Natriuretic peptides, such as B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), help gauge heart failure severity and prognosis. See BNP and NT-proBNP. - Electrocardiography: An ECG can identify prior myocardial injury, rhythm disturbances, and other cardiac conditions contributing to HFrEF. - Additional testing: Laboratory studies (renal function, electrolytes, liver enzymes), chest imaging, and, when indicated, coronary evaluation or cardiac magnetic resonance imaging to refine etiology and guide therapy. See renal function and cardiac magnetic resonance.
Classification by ejection fraction (EF) guides management and prognosis: - HFrEF: EF ≤40% - HFmrEF (mid-range): EF 41–49% - HFpEF (preserved): EF ≥50%
While the categories help organize care, many patients move between states over time with treatment and disease progression. See Heart failure with preserved ejection fraction for comparison.
Management
Management of HFrEF aims to relieve symptoms, slow disease progression, reduce hospitalization, and improve survival. A central element is guideline-directed medical therapy (GDMT), supplemented by device therapy, lifestyle modifications, and management of comorbidities. Treatment plans are individualized based on etiology, comorbid conditions, tolerability, and patient preferences. The discussion here emphasizes core, evidence-based principles and common clinical pathways.
Pharmacologic therapy
The backbone of GDMT in contemporary practice includes several drug classes with proven mortality and morbidity benefits:
Angiotensin-converting enzyme inhibitors or Angiotensin receptor blockers (or the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan as a single agent): These agents counteract maladaptive neurohormonal activation. In patients who tolerate it, switching from an ACE inhibitor to an ARNI is common to enhance outcomes. See ACE inhibitor and ARB; for the ARNIs, see sacubitril/valsartan.
Beta-blockers with proven benefit (for example, carvedilol, metoprolol succinate, and bisoprolol): These reduce heart rate and myocardial oxygen demand, with improvements in mortality and hospitalizations in stable patients. See beta-blocker.
Mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone: They reduce fluid retention and have separate benefits on mortality in appropriate patients, with monitoring for hyperkalemia and kidney function. See spironolactone and eplerenone.
SGLT2 inhibitors (such as dapagliflozin and empagliflozin): Originally diabetes medicines, these agents have demonstrated substantial benefits in reducing hospitalization for heart failure and cardiovascular mortality in patients with HFrEF, even without diabetes. See dapagliflozin and empagliflozin.
Additional agents: In selected patients, other drugs or combinations may be used, including hydralazine–isosorbide dinitrate in certain populations or circumstances. See hydralazine and isosorbide dinitrate.
Dyslipidemia management, anticoagulation when indicated (for atrial fibrillation or thromboembolism risk), and diuretics for symptom relief are components of comprehensive care. Diuretics (e.g., loop diuretics) help control congestion but have not shown a mortality benefit when used alone. See loop diuretic.
Therapy goals include achieving target or near-target doses, titrating as tolerated, and regular reassessment of renal function and electrolytes due to interdependencies among these medications. See guideline-directed medical therapy for heart failure.
Device and procedural therapies
For patients with persistent symptoms or high risk despite GDMT, device therapies and advanced interventions may be appropriate:
Implantable cardioverter-defibrillator (ICD) therapy to reduce risk of sudden cardiac death in certain patients with reduced EF and ischemic or non-ischemic cardiomyopathy. See implantable cardioverter-defibrillator.
Cardiac resynchronization therapy (CRT) to improve synchrony of ventricular contraction in patients with dyssynchronous heart failure and QRS prolongation. See cardiac resynchronization therapy.
In advanced cases, mechanical circulatory support such as a left ventricular assist device (LVAD) can be considered as a bridge to transplant or as destination therapy in select patients. See left ventricular assist device.
Revascularization procedures may be relevant where coronary disease drives the heart failure process. See revascularization.
Nonpharmacologic therapies and lifestyle
Sodium management and fluid balance: Dietary sodium restriction and careful fluid management help relieve edema and dyspnea for many patients. See sodium and fluid management.
Exercise and physical rehabilitation: Structured activity programs improve functional capacity and quality of life for many individuals with HFrEF. See exercise and cardiac rehabilitation.
Vaccination and infection prevention: Pneumococcal and influenza vaccines are recommended to reduce infectious complications. See vaccination.
Comorbidity management: Hypertension, diabetes, kidney disease, obesity, sleep apnea, and other conditions influence outcomes and require integrated care. See hypertension and diabetes mellitus.
Monitoring and follow-up
Ongoing follow-up focuses on symptom trajectory, weight and volume status, and laboratory parameters (especially renal function and electrolytes). Regular assessment helps guide medication titration and determine whether device therapy or additional interventions are warranted. See clinical monitoring.
Prognosis and epidemiology
prognosis in HFrEF varies with the underlying cause, comorbidities, and the degree to which GDMT is implemented and tolerated. Survival has improved substantially with modern therapies, though it remains a serious condition with risk of hospitalization and death, particularly in older patients or those with significant comorbidity. Broad population data consistently show that adherence to GDMT and appropriate device therapy are associated with better survival and fewer hospitalizations. See prognosis and mortality in heart failure.
Controversies and debates
In medical practice, several areas remain the subject of discussion among clinicians, researchers, and policy makers:
The sequencing and choice of GDMT: Whether to initiate with an ARNI versus ACE inhibitor and how to balance early introduction of SGLT2 inhibitors with monitoring for renal effects and electrolyte disturbances. See guideline-directed medical therapy.
Role of cost and access: The real-world uptake of advanced therapies like ARNIs and SGLT2 inhibitors can be limited by cost, insurance coverage, and regional disparities in health care delivery. This affects outcomes in practice and raises questions about how to optimize equity of care. See healthcare disparities.
Device therapy timing: The decision thresholds for ICD and CRT implantation may vary by region and by individual risk profiles, with ongoing discussion about which patients benefit most and when to pursue escalation to LVAD in advanced disease. See implantable cardioverter-defibrillator and cardiac resynchronization therapy.
Early palliative and QoL considerations: As with chronic diseases, balancing life-prolonging therapies with quality of life, symptom control, and patient preferences remains a nuanced topic in chronic HFrEF care. See palliative care.
Non-diabetic use of SGLT2 inhibitors: While trials have shown benefits in patients with and without diabetes, ongoing research continues to refine patient selection, dosing, and long-term safety in diverse populations. See dapagliflozin and empagliflozin.