Chronic Heart Failure

1. Clinical Overview

Summary

Chronic Heart Failure (CHF) is a complex clinical syndrome where the heart is unable to pump blood sufficient to meet the metabolic needs of the body (HFrEF) or can only do so at elevated filling pressures (HFpEF). It is the endpoint of all cardiovascular diseases and a major global pandemic affecting 1-2% of the adult population.

Historically viewed as a "pump failure" problem, it is now understood as a neurohormonal malignancy. Maladaptive activation of the Sympathetic Nervous System (SNS) and Renin-Angiotensin-Aldosterone System (RAAS) drives progressive cardiac remodelling, fibrosis, and death.

Survival has transformed in the last decade. We have moved from "Triple Therapy" to the "Four Pillars" of Guideline-Directed Medical Therapy (GDMT), which are now mandatory for all patients with HFrEF (LVEF less than 40%):

Beta-Blocker (Cardioselective).
ARNI (Sacubitril/Valsartan) or ACEi.
MRA (Spironolactone/Eplerenone).
SGLT2 Inhibitor (Dapagliflozin/Empagliflozin).

The classification is strictly based on Left Ventricular Ejection Fraction (LVEF):

Type	LVEF	Description
HFrEF	less than 40%	Heart Failure with Reduced Ejection Fraction. (The "Weak" Heart). Rich evidence base.
HFmrEF	41-49%	Mid-range (Mildly Reduced). "Grey Zone". Treat mostly as HFrEF.
HFpEF	≥50%	Preserved Ejection Fraction. (The "Stiff" Heart). Diastolic dysfunction. Driven by age/HTN/Obesity. Evidence limited (SGLT2i only).

Key Facts

Prevalence: 64 million people worldwide.
Prognosis: 5-year mortality is ~50% (Worse than Prostate, Breast, and Bowel cancer).
Prognostic Pillars: The "Four Pillars" reduce relative risk of death by ~60% combined.
Sudden Death: 50% of deaths in mild HF are sudden (Arrhythmic). 50% in severe HF are pump failure.
Iron Deficiency: Present in 50% of patients. Treating it (IV Iron) improves quality of life (but not survival).
Devices: ICDs prevent sudden death. CRT (Resynchronisation) improves pump function in LBBB.

Clinical Pearls

The "Symptoms vs Function" Pearl: LVEF correlates poorly with symptoms. A patient with LVEF 10% may be walking around (NYHA II), while LVEF 35% may be bedbound (NYHA IV). Treat the patient, not the number.

The "Titration" Pearl: "Start Low, Go Slow" is outdated. The new mantra is "Start Low, Go Fast". Every week of delay in starting the 4 pillars increases mortality risk. You should aim to initiate all 4 drugs within 4 weeks.

The "Creatinine" Pearl: Starting ACEi/ARNI/SGLT2i usually causes a dip in eGFR (up to 30%). This is hemodynamic, not structural injury. DO NOT STOP the drugs unless Creatinine rises > 50% or K+ > 5.5. This dip actually predicts better long-term renal preservation.

The "Heart Rate" Pearl: Heart rate is a modifiable risk factor. In Sinus Rhythm, every 10 bpm reduction prevents death. If Beta-Blocker is maxed and HR > 75, add Ivabradine.

2. Epidemiology

Burden of Disease

Prevalence: 1-2% of adults in developed countries. Rises to > 10% in over-70s.
Incidence: 5-10 per 1000 persons per year.
Hospitalisation: The #1 cause of hospitalisation in patients > 65.
Cost: Consumes 2-3% of total healthcare budgets (mostly inpatient costs).

Aetiology (Causes)

1. Ischaemic Heart Disease (IHD)

Most common cause (50%).
Post-MI scarring or chronic hibernation.
Action: Investigate for revascularisation.

2. Hypertension

Major cause of HFpEF and HFrEF.
LV Hypertrophy -> Stiffening -> Dilation -> Failure.

3. Valvular Disease

Aortic Stenosis (Pressure overload).
Mitral Regurgitation (Volume overload).

4. Dilated Cardiomyopathy (DCM)

Genetic: Titin (TTN) mutations (25% of familial cases).
Toxic: Alcohol ("Alcoholic Cardiomyopathy"), Chemotherapy (Anthracyclines/Herceptin), Cocaine.
Infective: Viral myocarditis (Coxsackie, Parvovirus, COVID-19).
Peripartum: Specific entity in late pregnancy.

5. Arrhythmia

Tachycardia-induced cardiomyopathy (e.g., uncontrolled AF). Reversible if rate controlled.

3. Pathophysiology

The Index Event & Remodelling

Insult: MI, Virus, or Pressure Load damages myocytes.
Compensatory Mechanisms (The "Double-Edged Sword"):
- SNS Activation: Adrenaline increases contractility and HR. (Good acute, toxic chronic).
- RAAS Activation: Angiotensin II causes vasoconstriction (maintains BP) and Aldosterone causes fluid retention (maintains Preload). (Good acute, causes fibrosis/congestion chronic).
Remodelling:
- LV Dilation (to maintain Stroke Volume via Starling Law).
- LV Sphericity (Heart becomes round, less efficient).
- Interstitial Fibrosis (Stiffening).
Decompensation: The compensatory mechanisms eventually fail, leading to fluid overload and low output.

The Neurohormonal Model

The basis of all modern therapy is blocking these toxic systems:

Beta-Blockers: Block Sympathetic toxicity.
ACEi/ARNI: Block Angiotensin II vasoconstriction/fibrosis.
MRA: Block Aldosterone fibrosis/retention.
SGLT2i: Complex mechanism (metabolic efficiency, osmotic diuresis, NHE1 inhibition).
Neprilysin Inhibition (Sacubitril): Enhances the "Good" system (Natriuretic Peptides) which promote vasodilation and natriuresis.

HFrEF vs HFpEF

HFrEF (Systolic): Loss of cardiomyocytes + Dilation. Eccentric hypertrophy. Pump problem.
HFpEF (Diastolic): Stiff cardiomyocytes + Fibrosis. Concentric hypertrophy. Filling problem.

Molecular Mechanisms

Calcium Handling: In failing myocytes, sarcoplasmic reticulum Calcium re-uptake is impaired (SERCA2a downregulation), leading to weak contraction and delayed relaxation.
Metabolic Shift: The failing heart switches from fatty acid oxidation (efficient) to glucose utilisation (inefficient), creating an energy-deprived state. SGLT2 inhibitors may restore metabolic balance by promoting ketone utilisation.

4. Clinical Presentation (NYHA)

The NYHA Classification

Describes functional capacity. Used to qualify for therapies (e.g., Entresto, ICD).

Class	Definition	Symptom Burden
I	No limitation of physical activity.	Asymptomatic (but has structural disease).
II	Slight limitation. Comfortable at rest.	Breathless on ordinary exertion (e.g., stairs, walking uphill).
III	Marked limitation. Comfortable at rest.	Breathless on less than ordinary exertion (e.g., dressing, walking on flat).
IV	Severe limitation.	Breathless at rest. Bedbound.

Symptoms

Left Sided Failure (Congestion):

Dyspnoea: Exertional breathlessness.
Orthopnoea: Number of pillows?
Paroxysmal Nocturnal Dyspnoea (PND): Waking up gasping. Specific for HF.
Fatigue: Low cardiac output.

Right Sided Failure (Congestion):

Ankle Swelling: Pitting oedema.
Abdominal Bloating: Ascites / Hepatic congestion.
Anorexia: Gut oedema causing early satiety.

ACC/AHA Stages (Progression)

Stage A: At risk (HTN/DM) but no structural disease.
Stage B: Structural disease (e.g., Previous MI/LVH) but NO symptoms. (Pre-HF).
Stage C: Structural disease + Symptoms. (Clinical HF).
Stage D: Refractory HF requiring advanced therapy (Transplant/VAD).

5. Clinical Examination

1. Inspection

Cachexia: "Cardiac Cachexia" (wasting) suggests advanced disease/poor prognosis.
Cyanosis / Pallor.

2. Pulse & BP

Pulse:
- Irregular? (AF is present in 40%).
- Low Volume? (Low output).
- Pulsus Alternans? (Beat-to-beat variation in severe failure - grave sign).
BP:
- Ideally low-normal (95-110 systolic) on treatment.
- High BP suggests undertreatment (especially in HFpEF).

3. Fluid Status (The "Dipstick" of the Heart)

JVP: The most useful sign. Elevated > 3cm.
- Hepato-jugular reflux: Press on liver, JVP rises. Early sign of congestion.
Oedema: Check ankles AND sacrum (if bedbound).
Weight: Check fluid charts.

4. Precordium

Apex Beat: Displaced (lateral and down) = Dilated LV.
S3 Gallop: "Ken-Tuck-Y". Rapid ventricular filling. Hallmark of HFrEF.
Murmurs:
- Pan-systolic (Apex): Functional Mitral Regurgitation (Dilated ring).
- Ejection Systolic (Base): Aortic Stenosis (Cause?).

5. Lungs

Bi-basal Crackles: Pulmonary oedema.
Pleural Effusion: Dullness at bases (Right side > Left side usually).

6. Investigations

Laboratory

NT-proBNP:
- Gold Standard Screening Test.
- Normal (less than 125 pg/ml) virtually excludes untreated HF.
- Elevated in: HF, AF, Renal Failure, Age, PE, Sepsis.
- Interpretation: If > 400, Refer for Echo. If > 2000, Urgent Referral.
U&Es: Baseline renal function and Potassium (crucial for RAASi initiation).
FBC: Anaemia precipitating failure?
Fe Studies: Ferritin/TSAT. (Iron deficiency is an independent target).
TFTs: Thyrotoxicosis? Myxoedema?

ECG (Electrocardiogram)

Normal ECG makes HFrEF very unlikely (Negative Predictive Value > 98%).
Look for:
- Q Waves (Old MI).
- LBBB (Left Bundle Branch Block) -> Candidate for CRT.
- LVH (Voltage criteria).
- AF.

Transthoracic Echocardiogram (TTE)

The definitive diagnostic test.

LVEF Assessment: Simpson's Biplane method.
Chamber Dimensions: LV End Diastolic Diameter (LVEDD).
Valve Function: Significant AS/MR?
Diastolic Function: E/A ratio, E/e'. (Crucial for HFpEF diagnosis).
Wall Motion: Regional (Ischaemia) vs Global (DCM).

Advanced Imaging

Cardiac MRI (CMR): Gold standard for volumes. Tissue characterisation (Scar vs Inflammation vs Amyloid vs Sarcoid).
Coronary Angiogram: To exclude ischaemic cause.
Nuclear Scintigraphy (DPD Scan): For Transthyretin Amyloidosis (ATTR-CM).

7. Management: The Four Pillars of GDMT

MANTRA: Diagnose HFrEF -> Start All 4 Pillars -> Titrate to Target. Do not wait for stability. In-hospital initiation is superior.

Pillar 1: Beta-Blockers

Block Sympathetic Toxicity. Reduce sudden death.

Agent	Starting Dose	Target Dose	Frequency
Bisoprolol	1.25 mg	10 mg	Daily (OD)
Carvedilol	3.125 mg	25 mg (less than 85kg)	Twice Daily (BD)
		50 mg (> 85kg)
Nebivolol	1.25 mg	10 mg	Daily (OD)
Metoprolol Succinate	12.5-25 mg	200 mg	Daily (OD)

Pillar 2: RAAS Inhibitors (ARNI / ACEi)

ARNI is preferred. ACEi if ARNI unavailable.

Agent	Starting Dose	Target Dose	Note
Sacubitril/Valsartan	24/26 mg BD	97/103 mg BD	Stop ACEi 36h before start.
Ramipril (ACEi)	1.25 - 2.5 mg OD	10 mg OD	Watch for cough.
Enalapril (ACEi)	2.5 mg BD	20 mg BD
Candesartan (ARB)	4 mg OD	32 mg OD	If cough with ACEi.

Pillar 3: MRA (Mineralocorticoid Receptor Antagonist)

Anti-fibrotic. Potassium sparing.

Agent	Starting Dose	Target Dose	Note
Spironolactone	25 mg OD	50 mg OD	Check K+ at 1 week.
Eplerenone	25 mg OD	50 mg OD	Less gynaecomastia.

Pillar 4: SGLT2 Inhibitor

Metabolic modulator. No titration needed.

Agent	Dose	Note
Dapagliflozin	10 mg OD	Do not start if eGFR less than 20.
Empagliflozin	10 mg OD	Watch for thrush.

Device Therapy (ICD & CRT)

Assess for device after 3 months of optimal medical therapy (OMT).

Device	Indication (NICE/ESC)	Purpose
ICD (Defibrillator)	Primary Prevention: LVEF less than 35%, NYHA II-III, Ischaemic Aetiology (post-MI > 40 days).	Prevents Sudden Cardiac Death (VT/VF).
CRT-P (Pacing)	LVEF less than 35%, Sinus Rhythm, LBBB (QRS > 130-150ms).	Resynchronises LV contraction. Improves Pump function and Symptoms.
CRT-D (Defib)	Meets criteria for both.	Both.

Advanced Therapies (Stage D)

For patients with refractory symptoms despite drugs and devices.

IV Inotropes: Milrinone/Dobutamine (Palliative or Bridge).
LVAD (Left Ventricular Assist Device):
- HeartMate 3: Continuous flow pump taken from LV apex to Aorta.
- Bridge to Transplant: Keeping patient alive until heart available.
- Destination Therapy: Permanent implant (if not transplant candidate).
- Life: No pulse! Management of BP relies on Doppler MAP (> 65).
Cardiac Transplantation: Gold standard. 10-year survival ~50%.

8. Non-Pharmacological Management

(Expanded Section)

1. Cardiac Rehabilitation

Structured exercise training is Class I Recommended.
Benefits: Improves functional capacity (VO2 max), QoL, and reduces hospitalisation.
Protocol: 3x weekly aerobic + resistance training. (Safe even in severe HF).

2. Diet and Lifestyle

Salt Restriction: less than 6g/day (approx 2g Sodium). Avoid adding salt at table.
Fluid Restriction: 1.5 - 2 Litres/day if congestion is a problem or Hyponatraemia present.
Alcohol: Strict abstinence if Alcohol-related cardiomyopathy. Moderate otherwise.
Weight: Obesity paradox exists (obese patients live longer?), but weight loss recommended if BMI > 35 to improve symptoms.
Vaccination: Annual Influenza and Pneumococcal (High risk of fatal pneumonia).

3. Holistic Care & Employment

A. Sexual Activity

Safe if the patient can climb two flights of stairs without stopping due to symptoms.
Drug Interaction: PDE5 inhibitors (Viagra/Sildenafil) are CONTRAINDICATED with Nitrates (causes potentially fatal severe hypotension). Safe with other HF meds.

B. Driving (UK DVLA Rules Example)

New Diagnosis: Stop driving for 1 month.
Group 1 (Car): May drive if symptoms controlled (NYHA I-III) and no distracting symptoms.
Group 2 (HGV): Usually disqualified if EF less than 40%.

C. Air Travel

Risk of DVT (stasis).
Hypoxia at altitude (Cabin pressure equivalent to 2000m).
If NYHA III/IV, may require in-flight oxygen.

9. Complications

Arrhythmias

Atrial Fibrillation: Frequent. Loss of atrial kick reduces Cardiac Output by 20%. Anticoagulation is mandatory (CHADSVASC score).
Ventricular Tachycardia: Common cause of syncope/death.

Renal Dysfunction (Cardio-Renal Syndrome)

Type 1: Acute HF causing AKI.
Type 2: Chronic HF causing CKD (Venous congestion + Low perfusion).
Hyperkalaemia: The "Achilles Heel" of RAASi therapy. Requires dietary restriction or K+ binders (Patiromer) to allow drug continuation.

Iron Deficiency

Defined as Ferritin less than 100 OR Ferritin 100-300 with TSAT less than 20%.
Functional iron deficiency common even without anaemia.
Treatment: IV Ferric Carboxymaltose (Ferinject) improves QoL (IRONMAN, AFFIRM-AHF).

Depression & Frailty

High prevalence > 20%. Reduces adherence.

10. Prognosis & Outcomes

Mortality Statistics

Around 50% mortality at 5 years after diagnosis.
After first admission for AHF: 1-year mortality ~30%.
Sudden Death risk is highest in milder HF (NYHA II).
Pump Failure death dominates in severe HF (NYHA IV).

Prognostic Models

MAGGIC Score: Meta-Analysis Global Group in Chronic Heart Failure.
- Variables: Age, EF, SBP, BMI, Creatinine, NYHA, Beta-blocker use, ACEi use.
Seattle Heart Failure Model: Predicts survival at 1, 2, 5 years.

Palliative Care

HF follows a "sawtooth" trajectory: Gradual decline punctuated by acute dips (admissions), never quite returning to baseline.
Advanced Care Planning: Discuss ceiling of care, ICD deactivation (at end of life to prevent shocking a dying heart), and preferred place of death.
Symptom Control:
- Dyspnoea: Low dose Morphine (2.5mg PRN) reduces air hunger.
- Anxiety: Lorazepam.

11. Evidence & Guidelines

Guidelines

ESC (2021) Guidelines for Acute and Chronic Heart Failure.
- Established the "Four Pillars" as Class I recommendations.
- Simplified algorithm.
AHA/ACC/HFSA (2022) Guidelines.
- Similar endorsement of SGLT2i and ARNI.

The "Big Three" Trials (Modern Era)

1. PARADIGM-HF (2014): ARNI vs ACEi.

Population: 8442 patients with HFrEF.
Comparison: Sacubitril/Valsartan (Entresto) vs Enalapril.
Result: Stopped early for benefit. 20% reduction in CV death or HF hospitalisation. 16% reduction in all-cause mortality.
Impact: ARNI replaced ACEi as Gold Standard. PMID: 25176015.

2. DAPA-HF (2019): Dapagliflozin in HFrEF.

Population: 4744 patients (With AND Without Diabetes).
Comparison: Dapagliflozin 10mg vs Placebo.
Result: 26% reduction in primary composite outcome. NNT = 21. Consistent across non-diabetics.
Impact: SGLT2i became a heart drug, not just a sugar drug. PMID: 31535829.

3. EMPEROR-Reduced (2020): Empagliflozin in HFrEF.

Population: 3730 patients (More severe HF than DAPA).
Result: 25% reduction in primary outcome. Slowed decline in eGFR.
Impact: Confirmed class effect of SGLT2i. PMID: 32865377.

Historical Foundation Trials

SOLVD (1991): Enalapril reduced mortality by 16%. (First proof of RAASi benefit).
Merit-HF (1999): Metoprolol reduced mortality by 34%.
CIBIS-II (1999): Bisoprolol reduced mortality by 34%.
RALES (1999): Spironolactone reduced mortality by 30% in severe HF.
SHIFT (2010): Ivabradine reduced hospitalisation in HR > 70.
DANISH (2016): Non-ischaemic cardiomyopathy ICDs did not show mortality benefit (but reduced sudden death).

12. Patient Explanation

What is Heart Failure?

It doesn't mean your heart has stopped. It means your heart is weaker than normal and struggles to pump blood around the body efficiently. This causes fluid to back up (congestion), making you breathless and causing swollen ankles.

How do we treat it? (The "Armour")

We cannot "cure" the weakness (unless we do a transplant), but we can strengthen the heart and protect it. Think of your treatment as a suit of armour with four plates:

Beta-Blocker: Slows the heart down to let it fill better and rest.
ACE/ARNI: Relaxes blood vessels so the heart doesn't have to push as hard.
MRA: Stopping salt retention and stiffening.
SGLT2 (Flozin): Improves fuel efficiency of the heart.

You need ALL FOUR to be fully protected.

What can I do?

Weigh yourself daily: If you gain > 2kg in 2-3 days, it is fluid, not fat. Call your nurse.
Watch your fluid: Limit intake to 1.5 - 2 Litres a day.
Limit Salt: Don't add salt to meals.
Exercise: It is safe and recommended! Join a cardiac rehab class.

13. References

Guidelines

McDonagh TA et al (ESC). 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. PMID: 34447992

Medical Therapy Trials

McMurray JJ et al (PARADIGM-HF). Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. PMID: 25176015
McMurray JJ et al (DAPA-HF). Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. PMID: 31535829
Packer M et al (EMPEROR-Reduced). Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. PMID: 32865377
Pitt B et al (RALES). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999 Sep 2;341(10):709-17. PMID: 10471459
CIBIS-II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999 Jan 2;353(9146):9-13. PMID: 10023943
MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999 Jun 12;353(9169):2001-7. PMID: 10376614
Swedberg K et al (SHIFT). Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. PMID: 20801500
Anker SD et al (EMPEROR-Preserved). Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. PMID: 34449189
Kober L et al (DANISH). Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016 Sep 29;375(13):1221-30. PMID: 27571011

14. Examination Focus

Common Exam Questions

"What conditions decrease BNP despite Heart Failure?"
- Answer: Obesity (High BMI degrades BNP). Flash Pulmonary Oedema (BNP hasn't had time to rise).
"Criteria for CRT?"
- Answer: LVEF less than 35%, NYHA II-IV, Sinus Rhythm, LBBB with QRS > 130ms.
"Patient on Ramipril develops cough. Next step?"
- Answer: Switch to ARB (Candesartan/Valsartan). Cough is bradykinin mediated (ACE specific).
"Which beta-blockers are licensed for HF?"
- Answer: Bisoprolol, Carvedilol, Metoprolol Succinate (Not Tartrate!), Nebivolol. Atenolol is NOT licensed/effective.

Viva Points

The 4 Pillars: Be able to reel them off and cite the trials (PARADIGM, DAPA/EMPEROR, CIBIS/MERIT, RALES).
Device Therapy: Explain why we don't put ICDs in everyone (Cost vs Benefit, NNT).
SGLT2i Mechanism: Be honest - "We don't fully know, but it's not just glucose".

Last Reviewed: 2026-01-04 | MedVellum Editorial Team