Heart Failure
Classification: A dynamic clinical syndrome caused by structural and/or functional cardiac abnormalities that impair filling, ejection, or both and may progress, stabilize, improve, or enter remission over time.
Key diagnostic discriminator: HFrEF is dominated by impaired systolic function; HFpEF is characterized by clinical heart failure with preserved EF and evidence of elevated filling pressures or abnormal diastolic function.
Clinical priority: Understand how compensatory mechanisms preserve perfusion initially yet drive congestion, fibrosis, hypertrophy, and remodeling when chronically activated.
Etiology and Clinical Phenotypes
Heart failure is a final common syndrome produced by many diseases. Important etiologic categories include ischemic myocardial injury, chronic hypertension, valvular disease, cardiomyopathy, myocarditis or infiltrative disease, and persistent tachy- or bradyarrhythmias. Most HF is a low-output state caused by impaired cardiac function. High-output HF is different: cardiac output may be elevated, yet it remains inadequate for unusually high metabolic or circulatory demand, as can occur in conditions such as severe anemia, thyrotoxicosis, large arteriovenous shunts, or early distributive states (Ng & Yeung, 2026; Norris, 2020).
HF phenotypes also include HF with mildly reduced EF (HFmrEF) and HF with improved EF (HFimpEF). HFimpEF describes a patient with prior reduced EF whose EF subsequently improves; improvement in EF does not necessarily mean the underlying myocardial disease has resolved (Heidenreich et al., 2022; Ng & Yeung, 2026; Walsh et al., 2026).
HFrEF and HFpEF
The 2022 AHA/ACC/HFSA guideline uses LVEF ≤40% for HFrEF, 41%–49% for HFmrEF, and ≥50% for HFpEF, with HFpEF requiring clinical heart failure plus objective evidence of elevated filling pressures or structural/functional cardiac abnormality. The 2026 Second Universal Definition deliberately moves away from rigid EF cutoffs and emphasizes reduced, preserved, and improved EF phenotypes within a dynamic disease trajectory; the numeric ranges here are retained as the 2022 U.S. guideline treatment-classification thresholds (Heidenreich et al., 2022; Walsh et al., 2026).
In HFrEF, myocardial injury or dysfunction reduces stroke volume and often promotes dilation. In HFpEF, hypertrophy, fibrosis, infiltrative disease, extracellular-matrix changes, and microvascular dysfunction increase ventricular stiffness and slow relaxation, causing high filling pressures despite a relatively preserved EF (Ng & Yeung, 2026).
| Feature | HFrEF | HFpEF |
| Dominant defect | Impaired contraction | Impaired relaxation/compliance |
| Typical LVEF | ≤40% | ≥50% with objective evidence of HF physiology |
| Typical remodeling | Often dilation | Often hypertrophy/stiffness |
| Common consequence | Low output + congestion | High filling pressure + congestion |
Adaptive and Maladaptive Mechanisms
Frank-Starling recruitment increases contractile force as preload rises, but once the failing ventricle reaches the flatter portion of the curve, additional preload raises filling pressure without meaningfully increasing output (Ng & Yeung, 2026; Norris, 2020).
Sympathetic activation increases heart rate, contractility, and vascular tone. Chronically, this increases oxygen demand, arrhythmia risk, afterload, and myocyte injury. Reduced renal perfusion activates RAAS; angiotensin II increases vasoconstriction and remodeling, while aldosterone promotes sodium-water retention and fibrosis (Ng & Yeung, 2026; Norris, 2020).
ANP and BNP counter RAAS and sympathetic signaling through natriuresis, diuresis, and vasodilation. Endothelins promote vasoconstriction and hypertrophy. Ventricular hypertrophy and remodeling initially normalize wall stress but eventually worsen oxygen demand, compliance, geometry, and mechanical efficiency (Norris, 2020; Ng & Yeung, 2026).
| Mechanism | Short-term benefit | Long-term consequence |
| Frank-Starling | Raises stroke volume | High filling pressure/congestion |
| SNS | Supports HR, contractility, BP | Oxygen demand, arrhythmia, myocyte injury |
| RAAS | Supports pressure and circulating volume | Afterload, fluid retention, fibrosis |
| Hypertrophy/remodeling | Reduces wall stress initially | Stiffness, dilation, inefficient geometry |
| Natriuretic peptides | Natriuresis/vasodilation | Counterregulation becomes insufficient |
Congestion and Hypoperfusion
Left-sided HF raises LV and left atrial filling pressures, transmitting pressure backward to the pulmonary circulation and causing exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, crackles, or pulmonary edema. Right-sided dysfunction elevates systemic venous pressure, causing JVD, peripheral edema, hepatomegaly, ascites, abdominal congestion, and weight gain (Ng & Yeung, 2026; Norris, 2020).
Forward failure produces fatigue, cool extremities, altered cognition, reduced urine output, and hypotension when tissue perfusion becomes inadequate (Ng & Yeung, 2026; Norris, 2020).
Chronic Heart Failure Versus Acute Decompensation
Chronic HF reflects persistent structural or functional disease with a relatively stable balance between cardiac dysfunction and compensatory mechanisms. Acute decompensated HF occurs when filling pressures, congestion, or perfusion worsen over hours to days, often because of ischemia, arrhythmia, uncontrolled blood pressure, infection, medication or dietary factors, renal deterioration, or progression of the underlying cardiac lesion. A patient may therefore have chronic remodeling but present with an acute hemodynamic syndrome. The immediate assessment is whether the dominant problem is congestion, hypoperfusion, or both (Ng & Yeung, 2026; Norris, 2020).
Diagnostic Approach
- Use history and examination to identify congestion, hypoperfusion, precipitating disease, and functional limitation (Ng & Yeung, 2026; Norris, 2020).
- Transthoracic echocardiography evaluates EF, chamber size, wall motion, hypertrophy, valve function, diastolic function, and pericardial disease (Ng & Yeung, 2026; Norris, 2020).
- BNP or NT-proBNP supports diagnosis and hemodynamic assessment when interpreted with clinical and imaging findings (Ng & Yeung, 2026; Norris, 2020).
- Evaluate renal function, electrolytes, CBC, ECG, and chest imaging as clinically indicated (Ng & Yeung, 2026; Norris, 2020).
Findings That Argue Against Heart Failure as the Primary Cause
No single finding excludes heart failure, but another diagnosis becomes more likely when dyspnea occurs without structural/functional cardiac abnormality or congestion, edema is better explained by heavy protein loss or cirrhosis, or the presentation is dominated by primary pulmonary, infectious, hemorrhagic, or other systemic disease. Heart failure can coexist with these conditions (Ng & Yeung, 2026).
Differential Diagnosis
Important alternatives or coexisting conditions include COPD or asthma, pulmonary embolism, pneumonia, nephrotic syndrome or advanced kidney disease, cirrhosis, severe anemia, and pericardial disease. The distinction depends on evidence of cardiac structure/function, filling pressures, congestion, and the competing disease process (Ng & Yeung, 2026).
Treatment Principles
Treatment logic follows the pathophysiology: relieve clinically important congestion, reduce maladaptive neurohormonal activation and afterload, limit remodeling, treat the underlying cause and precipitating factors, and preserve renal and end-organ perfusion. Current HFrEF therapy specifically targets pathways that become harmful when chronically activated, while HFpEF management is driven by the HF phenotype, congestion, and contributing comorbidities (Heidenreich et al., 2022; Walsh et al., 2026).
Red Flags
- Acute pulmonary edema or severe hypoxemia (Ng & Yeung, 2026; Norris, 2020).
- Cardiogenic shock, new hypotension, cool extremities, or altered mental status from hypoperfusion (Ng & Yeung, 2026; Norris, 2020).
- Rapidly worsening renal function, severe electrolyte abnormality, or escalating congestion (Ng & Yeung, 2026; Norris, 2020).
- New ischemic symptoms or a severe arrhythmia precipitating decompensation (Heidenreich et al., 2022; Ng & Yeung, 2026).
High-Yield Distinctions
- Heart failure is not synonymous with reduced EF.
- A preserved EF does not exclude severe elevation in filling pressure.
- Symptoms arise from congestion, hypoperfusion, or both.
- Compensatory SNS and RAAS activation becomes a driver of disease progression when persistent.
- HF and kidney dysfunction can reinforce one another through low perfusion, venous congestion, and sodium-water retention.
Related YourDNP Resources
- Cardiac Pathophysiology Foundations
- Arrhythmias
- Acute Kidney Injury
- Chronic Kidney Disease
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References
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Ng, T. M. H., & Yeung, S. L. (2026). Heart failure. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.
Walsh, M. N., Kober, L., Sliwa, K., Adamo, M., Agarwal, A., Banerjee, A., Bozkurt, B., Cikes, M., Damasceno, A., Desai, A. S., Felker, G. M., Hogan, G., Kinugawa, K., Kittleson, M., Lam, C. S. P., McDonagh, T., Metra, M., Mullens, W., Ribeiro, A. L. P., … Vest, A. (2026). AHA/ACC/ESC/WHF expert consensus document: Second universal definition of heart failure (2026). Circulation, 154(7), e279–e293. https://doi.org/10.1161/CIR.0000000000001455