Heart Failure (Adult)

1. Overview

Heart Failure (HF) is a complex clinical syndrome characterised by the heart's inability to maintain sufficient cardiac output to meet metabolic demands, or doing so only at elevated filling pressures. It is the final common pathway for most cardiac diseases and remains the leading cause of hospitalisation in adults over 65. Historically a "death sentence," the 21st-century management of HF has been transformed by neurohormonal blockade and targeted metabolic therapies. [1]

The syndrome is defined by a constellation of symptoms (dyspnoea, fatigue) and signs (oedema, raised JVP) resulting from structural or functional cardiac abnormalities. Modern classification is anchored in the Left Ventricular Ejection Fraction (LVEF): HFrEF (Reduced, ≤40%), HFmrEF (Mildly Reduced, 41-49%), and HFpEF (Preserved, ≥50%). [2]

Management has shifted from a sequential "step-up" approach to a rapid initiation of the "Four Pillars" of guideline-directed medical therapy (GDMT) within weeks of diagnosis, a strategy proven to significantly reduce 90-day readmissions and mortality. [3]

2. Epidemiology

Global Distribution

HF affects over 64 million people worldwide. While incidence is stabilising in high-income countries due to better management of IHD and hypertension, prevalence is rising due to an ageing population and improved survival after myocardial infarction. [4]

Mortality Risk

The "Cancer Comparison": Advanced HF carries a 5-year mortality rate (~50%) that is worse than many common malignancies, including breast and prostate cancer. [5]

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3. Aetiology & Pathophysiology

⚠️ THE 7-STEP MOLECULAR MECHANISM

1. The Index Insult: A primary event (MI, pressure/volume overload, or toxin) causes the loss of functional myocytes or impairs their contractility.
2. Neurohormonal Trigger: Falling cardiac output triggers the arterial baroreceptors to unload, activating the Sympathetic Nervous System (SNS) and the Renin-Angiotensin-Aldosterone System (RAAS).
3. Adrenergic Toxicity: Chronic SNS activation leads to chronic exposure to high norepinephrine levels. This causes β1-receptor downregulation and direct cardiomyocyte toxicity (Ca2+ overload and apoptosis).
4. RAAS-Mediated Fibrosis: Angiotensin II acts on AT1 receptors, stimulating TGF-β. This promotes the transition of fibroblasts to myofibroblasts, leading to collagen deposition and stiffening of the myocardium (remodelling).
5. Neprilysin Counter-Regulation: The body attempts to compensate via Natriuretic Peptides (ANP, BNP). However, these are rapidly degraded by the enzyme neprilysin. The imbalance between the "destructive" RAAS/SNS and the "protective" Natriuretic system drives progression.
6. SGLT2 & Metabolic Derangement: Failing hearts shift from fatty acid oxidation to inefficient glucose metabolism. The loss of metabolic flexibility and myocardial "starvation" precipitates pump failure.
7. Decompensation & Vicious Cycle: Elevated filling pressures lead to pulmonary and systemic congestion, which impairs renal function (Cardiorenal Syndrome Type 1), further activating RAAS and creating a lethal positive feedback loop. [6]

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4. Clinical Presentation

Symptoms

• Dyspnoea on Exertion (DOE): Most sensitive (95%).
• Orthopnoea: Need for multiple pillows (highly specific).
• Paroxysmal Nocturnal Dyspnoea (PND): Sudden waking with gasping (highly specific).
• Fatigue: Reduced cardiac output and skeletal muscle hypoperfusion.

Physical Signs

1. Elevated JVP: Most specific sign of fluid overload (> 4 cm above sternal angle).
2. S3 Gallop: Low-frequency sound in early diastole; indicates a dilated LV with high filling pressures.
3. Displaced Apex Beat: Evidence of cardiomegaly (displaced laterally and inferiorly).
4. Bibasal Crackles: Pulmonary oedema (often absent in chronic HF due to lymphatic compensation).
5. Peripheral Oedema: Pitting oedema (ankles, legs, sacrum).

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5. Investigations

First-Line

• NT-proBNP/BNP: The "Rule Out" test.
  • Acute: NT-proBNP less than 300 pg/mL excludes HF (NPV > 98%).
  • Chronic: NT-proBNP less than 125 pg/mL excludes HF.
• 12-Lead ECG: Look for LBBB (CRT candidate), prior Q-waves (IHD), or AF.
• Chest X-Ray: Cardiomegaly, Kerley B lines, pleural effusions.

The Gold Standard

• Transthoracic Echocardiogram (TTE): Essential for categorisation (HFrEF/HFpEF), valvular assessment, and measuring wall stress.

Advanced Imaging

• Cardiac MRI (CMR): The "gold standard" for tissue characterisation (ischaemic scar vs. non-ischaemic fibrosis) and viability assessment.

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6. Management: The "Four Pillars" Revolution

Management has moved away from the sequential approach to Triple/Quadruple therapy within 4 weeks of diagnosis. [7]

Pillar 1: ARNI (Sacubitril/Valsartan)

• Mechanism: Neprilysin inhibition (increases BNP) + AT1 blockade.
• Trial: PARADIGM-HF showed 20% reduction in CV death vs. Enalapril.
• Pearl: Must have a 36-hour washout if switching from an ACE inhibitor to avoid angioedema.

Pillar 2: Beta-Blocker (Bisoprolol/Carvedilol)

• Mechanism: Blocks adrenergic toxicity and reduces heart rate (prolonging diastole).
• Trial: CIBIS-II / MERIT-HF.
• Pearl: Do NOT stop in acute decompensation unless the patient is in cardiogenic shock.

Pillar 3: MRA (Spironolactone/Eplerenone)

• Mechanism: Antagonises aldosterone-mediated fibrosis.
• Trial: RALES.
• Pearl: Gynaecomastia is common with spironolactone; switch to Eplerenone if this occurs.

Pillar 4: SGLT2 Inhibitor (Dapagliflozin/Empagliflozin)

• Mechanism: Osmotic diuresis + myocardial metabolic switch + reduced preload/afterload.
• Trial: DAPA-HF / EMPEROR-Reduced.
• Pearl: Effective even in non-diabetic patients.

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7. HFpEF Management (The Preserved Challenge)

HFpEF (EF ≥50%) was once untreatable.

• First-line: SGLT2 inhibitors (EMPEROR-Preserved / DELIVER).
• Weight Loss: STEP-HFpEF trial showed Semaglutide (GLP-1) significantly improves symptoms and exercise capacity in obese HFpEF patients. [8]

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8. Device Therapy (When Drugs Are Not Enough)

• ICD (Defibrillator): Primary prevention of Sudden Cardiac Death (SCD) if EF ≤35% despite 3 months of GDMT.
• CRT (Biventricular Pacing): Indicated if EF ≤35% and LBBB (QRS > 130-150ms). Resynchronises the septum and lateral wall.
• LBBP (Left Bundle Branch Pacing): Emerging "physiological" pacing technique superior to traditional CRT in some cohorts.

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9. Complications

1. Cardiorenal Syndrome: Reciprocal injury to kidneys.
2. Cardiac Cachexia: Loss of > 5% body weight; poor prognostic marker.
3. Tachycardiomyopathy: AF with rapid ventricular response causing EF drop.
4. Sudden Cardiac Death: 50% of HFrEF deaths are arrhythmic.

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10. Evidence: Landmark Trials

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11. Single Best Answer (SBA) Questions

Question 1

A 70-year-old male with HFrEF (EF 30%) is on Ramipril 10mg and Bisoprolol 10mg. He remains symptomatic (NYHA III). BP is 115/75, K+ 4.2. What is the most appropriate medication to add next?

• A) Digoxin
• B) Ivabradine
• C) Spironolactone
• D) Furosemide
• E) Amlodipine
• Answer: C. MRAs (Spironolactone) are one of the "Four Pillars" and have a proven mortality benefit. They should be added before symptoms-only drugs like Digoxin.

Question 2

A patient is being switched from Enalapril to Sacubitril/Valsartan. How long must you wait between the last dose of Enalapril and the first dose of the new drug?

• A) 12 hours
• B) 24 hours
• C) 36 hours
• D) 48 hours
• E) No wait required
• Answer: C. A 36-hour washout period is mandatory to prevent bradykinin accumulation and the risk of life-threatening angioedema.

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12. Viva Scenario: The "Cold and Wet" Patient

Examiner: "A patient with HFrEF is admitted with worsening breathlessness. On examination, they have basal crackles, but their peripheries are cold to the touch and their SBP is 85 mmHg. What is the haemodynamic profile and management?"

Candidate:

1. Haemodynamic Profile: This is a "Cold and Wet" profile, indicating Cardiogenic Shock (congestion + hypoperfusion).
2. Management:
   • Stabilisation: High-flow O2, sit upright, escalate to CCU/ICU.
   • Inotropes: Dobutamine or Milrinone to increase CO.
   • Diuresis: Careful IV loop diuretics once perfusion is supported.
   • Mechanical Support: Consider IABP or Impella if refractory.
   • Avoid: Do NOT give beta-blockers in this acute shocked state.

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13. References

1. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021. [PMID: 34447992]
2. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022. [PMID: 35363499]
3. Mebazaa A, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF). Lancet. 2022. [PMID: 36356616]
4. Kosiborod MN, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (STEP-HFpEF). N Engl J Med. 2023. [PMID: 37622681]
5. McMurray JJ, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF). N Engl J Med. 2014. [PMID: 25176015]

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Last Updated: 2026-01-05 | MedVellum Editorial Team