Heart Failure

Terminology:

Asymptomatic (Stage B) Left-Ventricular Systolic Dysfunction

• Definition: LVEF < 40 % or other structural/functional LV abnormality without prior or current HF symptoms.
• Clinical importance:
  • Annual risk of progressing to overt HF ≈ 5 – 10 %;
  • justifies ACE-I/ARNI ± β-blocker even when asymptomatic.

New-Onset (De Novo) Heart Failure

• Definition: First clinical presentation of HF in a patient with no previous HF diagnosis.
• Presentation window: Symptoms may be abrupt (hours) or insidious (weeks).
• Treatment status: Patient has not yet received guideline-directed HF therapy.

Chronic (Established) Heart Failure

• Definition: HF diagnosed ≥ 3 months ago with ongoing management.
• Course: May be stable, progressively worsening, or intermittently decompensated.

Acute Heart Failure

• Umbrella term for rapid onset or major exacerbation of HF signs/symptoms requiring urgent therapy.
  • Cardiogenic Pulmonary Oedema (APO):
    • Minutes–hours onset of severe dyspnoea, pink frothy sputum, rales;
    • CXR: alveolar flooding.
  • Cardiogenic Shock:
    • SBP < 90 mmHg (or need for vasopressors) plus
      • CI < 2.2 L min-¹ m⁻²
      • PCWP > 15 mmHg
      • serum lactate > 2 mmol L⁻¹
      • end-organ hypoperfusion.
  • Acute Decompensated HF (ADHF):
    • Gradual days–weeks rise in congestion on a background of chronic HF (“wet & warm” most common profile).

HFrEF, HFmrEF, and HFpEF

on-fraction phenotype	LVEF cut-off (ESC 2023 / ACC-AHA-HFSA 2022)	Where it sits in the terminology hierarchy	Key implications
HFrEF (Heart Failure with Reduced EF)	< 40 %	• Applies once a patient meets any symptomatic category (new-onset, acute, chronic, ADHF, APO, cardiogenic shock, etc.). • “Asymptomatic LV dysfunction” with EF < 40 % = Stage B (pre-HF).	• Robust evidence for GDMT: ACE-I/ARNI, β-blocker, MRA, SGLT2i ± CRT/ICD. • EF threshold (<40 %) also determines device candidacy.
HFmrEF (Heart Failure with Mildly Reduced EF)	40 – 49 %	• Same temporal labels (new-onset, acute, chronic) still apply; this is simply the EF phenotype. • If asymptomatic it still falls under Stage B.	• Often behaves biologically like HFrEF; guidelines recommend similar core pharmacotherapies, albeit with weaker evidence.
HFpEF (Heart Failure with Preserved EF)	≥ 50 % plus structural heart disease and/or diastolic dysfunction and raised natriuretic peptides	• Again, temporal descriptors (new-onset, acute, chronic) are layered on top of the EF phenotype. • If EF ≥ 50 % but patient is asymptomatic → not HF; if Natriuretic peptides elevated with symptoms → HFpEF Stage C.	• Pharmacologic options fewer (SGLT2i now class I in ESC 2023; MRA, ARNi class IIb). • Management focuses on BP control, weight/AF/CKD optimisation, diuretics for congestion.

Right-Sided Heart Failure

• Definition: Predominant or isolated inability of the right ventricle to deliver blood to the pulmonary circulation.
• Common causes:
  • Secondary to left-sided HF (most frequent)
  • Pulmonary hypertension (idiopathic, chronic lung disease, thromboembolic)
  • RV infarction, severe tricuspid or pulmonic valve disease, congenital heart disease.
• Prognosis: Advanced RHF indicates poor outcomes; management targets underlying aetiology and afterload reduction.

---

New York Heart Association functional classification of heart failure
Class I	Class II	Class III	Class IV
No limitation of ordinary physical activity	Slight limitation of ordinary physical activity No symptoms at rest	Marked limitation of ordinary physical activity No symptoms at rest	Symptoms on any physical activity or at rest

Classification

• classified according to the LVEF 
• LVEF is the global measure of LV contractility and reflects the percentage of ventricular volume that is ejected per heartbeat.
• The lower limit of normal for the LVEF is 50–55%.

EF = (EDV − ESV)/EDV (expressed as a percentage)

where EF = ejection fraction; EDV = end diastolic volume; ESV = end systolic volume.

Heart failure classified by ejection fraction: – HFrEF (<40%) vs HFpEF (≥50%). – This distinction guides treatment, prognosis, and resource use. – HFrEF has strong evidence for medications that improve survival (e.g. ACEi, β-blockers, SGLT2i). – HFpEF lacks proven mortality-reducing drugs, though SGLT2i now offer benefit. Device therapy (e.g. ICD, CRT) is indicated only in HFrEF. – HFpEF diagnosis is more complex, needing signs of diastolic dysfunction or structural disease. – Symptoms alone aren’t enough in HFpEF—many elderly patients may be misdiagnosed. Misclassification can lead to inappropriate treatment or missed opportunities. – PBS-funded drugs (e.g. ARNI) require HFrEF-specific criteria. – Accurate subtyping improves patient education, treatment planning, and health outcomes.
HFrEF	HFpEF (Preserved Ejection Fraction)
Symptoms ± signs of heart failure Symptoms ± signs of heart failure LVEF < 40% No further structural or diastolic testing needed NT-proBNP usually elevated but not mandatory for diagnosis	1) Symptoms ± signs of heart failure 2) LVEF ≥ 50% Objective evidence of cardiac dysfunction: – Structural abnormality: Left ventricular hypertrophy (LVH) or Left atrial enlargement (LAE) OR – functional abnormality: Diastolic dysfunction (e.g., E/e′ >15, reduced e′ velocity) Elevated filling pressures (invasively or via echo) 3) Elevated NT-proBNP/BNP 4) Positive exercise stress testing

BNP/NT −proBNP diagnostic cut-off values
	BNP (ng/L)	NT proBNP (ng/L)
Heart failure rule-out	<100	<300
Heart failure rule-in	>400	Age <50 yr: >450 Age 50–75 yr: >900 Age >75 yr: >1800

---

Pathophysiology

Heart Failure with Reduced Ejection Fraction (HFrEF)

Definition:
HFrEF is characterised by impaired left ventricular systolic function, resulting in a reduced ejection fraction (EF <40%).

Pathophysiological Mechanisms:

• Primary mechanism: Impaired myocardial contractility → ↓ Stroke volume → ↓ Cardiac output
• Consequences:
  1. Reduced end-organ perfusion
     • Leads to fatigue, renal hypoperfusion, altered mental state
  2. Neurohormonal activation:
     • Sympathetic nervous system (SNS): ↑ Heart rate and contractility (initial compensation)
     • Renin–angiotensin–aldosterone system (RAAS): Promotes sodium and water retention → volume overload
     • Natriuretic peptide system: Blunted compensatory response
  3. Ventricular remodelling:
     • Left ventricular dilatation
     • Myocyte hypertrophy
     • Myocardial fibrosis
       → Structural and functional deterioration of the myocardium
  4. Progressive worsening of systolic function:
     • Positive feedback loop → ↑ wall stress and energy demand → ↓ cardiac reserve

Heart Failure with Preserved Ejection Fraction (HFpEF)

Definition:
HFpEF is characterised by clinical features of heart failure despite a preserved ejection fraction (EF ≥50%), with normal or near-normal systolic function but impaired diastolic filling.

Epidemiology & Patient Profile:

• Commonly seen in:
  • Older adults
  • Females
  • Patients with hypertension, obesity, type 2 diabetes, atrial fibrillation, and chronic kidney disease

Proposed Pathophysiological Mechanisms:

1. Systemic comorbidities (e.g. HTN, DM, obesity) →
   Chronic systemic inflammation →
   Coronary microvascular endothelial dysfunction →
   ↓ Nitric oxide and ↓ cGMP →
   Hypophosphorylation of titin →
   ↓ Myocardial relaxation + ↑ Myocardial fibrosis →
   ↓ LV compliance (stiff ventricle)
2. Diastolic dysfunction:
   • Impaired LV relaxation
   • Elevated LV filling pressures despite preserved EF
3. Increased LV afterload:
   • Arterial stiffening with age and hypertension
   • Leads to early return of reflected pulse wave → ↑ Systolic pressure and LV workload
4. Abnormal peripheral oxygen extraction:
   • Reduced skeletal muscle perfusion and mitochondrial dysfunction contribute to exercise intolerance
5. Subtle systolic and chronotropic dysfunction:
   • Reduced contractile reserve
   • Inadequate heart rate response during exertion

Feature	HFrEF (Reduced EF)	HFpEF (Preserved EF)
Definition	EF < 40%	EF ≥ 50% with heart failure symptoms
Primary Dysfunction	Systolic dysfunction – impaired contractility	Diastolic dysfunction – impaired ventricular relaxation and compliance
Ventricular Changes	LV dilation, wall thinning, eccentric hypertrophy	Concentric hypertrophy, increased wall stiffness
Cardiac Output	↓ Stroke volume and ↓ cardiac output	Often preserved at rest, limited reserve during stress
Neurohormonal Activation	SNS and RAAS activation → fluid retention, vasoconstriction	Similar but less pronounced than in HFrEF
Structural Remodelling	Myocyte loss, fibrosis, chamber dilation	Fibrosis, titin hypophosphorylation, arterial stiffening
Afterload	Increased due to neurohormonal vasoconstriction	Increased due to arterial stiffening and pulse wave reflection
Comorbidities	Often post-MI, dilated cardiomyopathy	Older age, hypertension, obesity, AF, diabetes, CKD
Inflammatory Role	Secondary to ischaemia and wall stress	Primary – microvascular inflammation from comorbidities
Peripheral Changes	Reduced perfusion, skeletal muscle wasting	Impaired oxygen utilisation, reduced chronotropic and contractile reserve
Typical Clinical Profile	Younger, male, often with known ischaemic heart disease	Older, female, with multiple comorbid conditions
Response to Therapy	Well-defined drug targets (ACEi, β-blockers, MRA, ARNI, SGLT2i)	Limited benefit from most HFrEF drugs; SGLT2i now emerging
Prognosis	Variable but improves with optimal medical therapy	Often chronic and progressive; limited treatment options

---

Causes of heart failure

Causes of heart failure
Myocyte damage or loss	Ischaemia: • infarction • ischaemia • microvascular disease • stunning or hibernation
	Inflammation: • infection (e.g., viral or Chagas disease) • immune (autoimmune and hypersensitivity myocarditis, and connective tissue disease)
	Toxic damage: • alcohol, cobalt • drugs—cytotoxic drugs (e.g., anthracyclines), stimulant drugs (e.g., amphetamines, cocaine), immunomodulating drugs (e.g., trastuzumab), clozapine, anabolic steroids • radiation
	Infiltration: • malignancy • amyloid/sarcoid • haemochromatosis or iron overload • glycogen storage diseases
	Endomyocardial pathology: • hypereosinophilic syndromes • endomyocardial fibrosis or fibroelastosis
	Metabolic abnormalities: • thyroid • growth hormone • cortisol • diabetes mellitus • phaeochromocytoma
	Nutritional abnormalities: • deficiencies (e.g., thiamine, selenium or iron) • malnutrition • obesity
	Genetic abnormalities: • dilated cardiomyopathy • hypertrophic cardiomyopathy • left ventricular noncompaction • arrhythmogenic right ventricular cardiomyopathy • muscular dystrophies • laminopathies
	Pregnancy and peripartum causes
Abnormal loading conditions	Hypertension
	Valve and myocardium: • valvular dysfunction (rheumatic and non-rheumatic) • congenital defects
	Pericardial pathology: • pericardial constriction or effusion
	High output states: • anaemia / sepsis / Arteriovenous fistula / thyrotoxicosis / Paget disease
	Volume overload: • renal failure • iatrogenic fluid overload
Arrhythmias	Tachyarrhythmias: • atrial (e.g., atrial fibrillation) • ventricular arrhythmias
	Bradyarrhythmias: • sinus node or atrioventricular node dysfunction

---

Diagnosis and Investigations

Causes of dyspnoea
Cardiac	• Increased left-sided intracavity filling pressure   – heart failure due to myocardial dysfunction (HFrEF, HFpEF)   – left-sided valvular dysfunction (aortic or mitral stenosis or regurgitation) • Myocardial ischaemia • Arrhythmia (tachyarrhythmia, bradyarrhythmia, ectopy, AF, atrioventricular disassociation) • Low cardiac output (left-sided):   – pulmonary hypertension   – hypovolaemia   – cardiac shunt   – cardiac compression (pericardial constriction, cardiac tamponade, tension pneumothorax)
Respiratory	• Hypoxia   – pulmonary parenchymal abnormality—infection (pneumonia), fibrosis, destruction (emphysema), oedema, alveolar haemorrhage and compression (pleural effusion and pneumothorax)   – airway obstruction (asthma, bronchitis, upper airway)   – ventilation–perfusion mismatch (pulmonary embolus and pulmonary shunt) • Central respiratory drive abnormality (pharmacological, metabolic) • Musculoskeletal respiration abnormality   – skeletal myopathy   – respiratory muscle fatigue   – chest wall abnormality (kyphoscoliosis, thoracic skeletal pain and obesity)
Peripheral muscle oxygen extraction abnormality or inefficiency	• Poor physical fitness • Myopathy • Neuromuscular disorders – Myasthenia Gravis, Amyotropic Lateral Sclerosis
Anxiety	• Panic attack, chronic anxiety state
Anaemia, iron deficiency
Hyperventilation	• Acidosis (renal failure, ketoacidosis, shock) • Pharmacological cause (that provoke Obstructive Lung Disease: Adenosine, Beta Blockers, NSAIDs or Aspirin) • Thyrotoxicosis

Acute Dyspnea in Adults (Mnemonic: PPOPPA)	Chronic Dyspnea in Adults (Duration >1 month)
Pulmonary Embolism Pulmonary Odema – Pulmonary: – Noxious gas inhalation, HAPE – Cardiogenic: Congestive Heart Failure Obstructed Airway (Foreign body, Epiglottitis) Pneumothorax (Spontaneous) Pneumonia Asthma or COPD	Obstructive Lung Disease (COPD, Asthma) Restrictive Lung Disease (Interstitial Lung Disease Kyphoscoliosis Neuromuscular disease (e.g. Myasthenia Gravis)) Congestive Heart Failure Pneumonia Anemia Myocardial Ischemia Hypothyroidism Upper airway conditions Obesity Psychiatric cause (e.g. Anxiety Disorder)
Dyspnea with Clear Lung Sounds	Airway Causes
Anemia Acute Coronary Syndrome Pericardial Tamponade Pulmonary Embolism Superior Vena Cava Syndrome Pulmonary Hypertension – Observe for signs of Right Heart Failure (edema, JVD) Metabolic Acidosis with compensatory Respiratory Alkalosis- Salicylate Toxicity presents with Tachypnea Anxiety Disorder – Diagnosis of exclusion	Foreign Body Aspiration Croup Epstein-Barr Virus Epiglottitis Bacterial Tracheitis Ludwig’s Angina Retropharyngeal Abscess Peritonsillar Abscess

History

• Dyspnoea(cardinal symptom)
• Orthopnoea
• exertional Dyspnoea
• benDopnoea
• paroxysmal nocturnal dyspnoea
• associated symptoms such as
  • chest pain
  • palpitations
  • dizziness
  • syncope
  • swollen ankles
  • abdominal bloating

Symptoms and signs of heart failure
More typical symptoms	More specific signs
Dyspnoea (usually with exertion) Orthopnoea Paroxysmal nocturnal dyspnoea Fatigue	Elevated jugular venous pressure Hepatojugular reflux Third heart sound Laterally displaced apex beat
Less typical symptoms	Less specific signs
Nocturnal cough Wheeze Abdominal bloating Anorexia Confusion (elderly) Depression Palpitations Dizziness Syncope Bendopnoea – (SOB when leaning forward)	Weight gain (>2 kg/wk) Weight loss (in advanced heart failure) Peripheral oedema (ankle, sacrum) Pulmonary crackles Pleural effusions Cardiac murmur Tachycardia Tachypnoea Cheyne–Stokes respiration Ascites

---

Cardiac Examination

• Heart Rate & Rhythm
  • Tachycardia (often compensatory)
  • Irregular rhythm if atrial fibrillation present
• Heart Sounds
  • S3 gallop – indicative of volume overload and poor compliance
  • S4 (if present) – stiff hypertrophic ventricle
• Murmurs
  • Functional mitral/tricuspid regurgitation due to annular dilatation
  • Coexisting valvular pathology (e.g., aortic stenosis)
• Apex Beat
  • Displaced inferolaterally – suggests cardiomegaly and left ventricular dilation
  • Heaving (pressure overload) or diffuse (volume overload)

luid Overload and Venous Congestion

• Jugular Venous Pressure (JVP)
  • Elevated JVP – hallmark of right-sided failure
  • Positive hepatojugular reflux – sustained rise in JVP >3 cm with abdominal pressure
• Peripheral Oedema
  • Bilateral pitting oedema in dependent areas (ankles, sacrum)
• Hepatic Congestion
  • Hepatomegaly – tender, pulsatile in severe tricuspid regurgitation
• Ascites
  • Suggests chronic right heart failure
• Weight Changes
  • Rapid weight gain indicates fluid retention

Respiratory Examination (Pulmonary Congestion)

• Auscultation
  • Bibasal fine crackles/rales – pulmonary oedema
  • Wheezing (“cardiac asthma”) in severe pulmonary congestion
• Percussion
  • Dullness in lung bases – suggests pleural effusion
• Inspection
  • Use of accessory muscles, tachypnoea
  • Increased anterior-posterior diameter in chronic lung disease

Perfusion & End-Organ Assessment

• Signs of Low Cardiac Output
  • Cool peripheries
  • Prolonged capillary refill time
  • Hypotension
  • Reduced urine output (if known)
• Neurologic
  • Confusion, lethargy – may reflect cerebral hypoperfusion

Peripheral Vascular Exam

• Pulse Quality
  • Weak or thready pulses – poor perfusion
• Pulsus paradoxus (if pericardial effusion suspected)
  • 10 mmHg systolic drop with inspiration

Other Relevant Systems

• Airway Exam
  • Generally not relevant unless upper airway obstruction suspected (e.g., stridor, peritonsillar abscess) – exclude unless clinically indicated
• Musculoskeletal
  • Severe chest wall abnormalities (e.g., pectus excavatum, kyphoscoliosis) – may affect cardiac/resp exam
• Skin
  • Cyanosis, pallor, or clubbing (suggests chronic hypoxia or alternative pathology)
• Psychomotor
  • Anxiety or restlessness can occur in hypoxia or sympathetic overactivity

---

Investigations

Labs 

• Basic investigations include
  • non-invasive measurement of oxygen saturation
  • 12-lead ECG
  • chest X-ray
  • serum biochemistry (electrolytes, renal function, and liver function)
  • full blood count
  • BNP or NT proBNP (e recommended for diagnosis in patients with suspected heart failure, when the diagnosis is uncertain – (Strong recommendation FOR; high quality of evidence))

Echo

• The single most useful investigation in patients with suspected or confirmed heart failure is the echocardiogram. 
• However, if the diagnosis is unclear and an echocardiogram cannot be arranged in a timely fashion, measurement of plasma BNP and NT proBNP has been shown to improve diagnostic accuracy.

BNP and NT-proBNP

Variability in Diagnostic Cut-offs

• Cut-off values for BNP and NT-proBNP differ across clinical trials.
• Levels are influenced by several patient-specific factors:
  • Age – levels rise with age
  • Renal function – chronic kidney disease increases baseline levels
  • Body habitus – lower levels in obese individuals
• Pragmatic rule-out thresholds:
  • BNP < 100 ng/L
  • NT-proBNP < 300 ng/L
  • Useful for excluding heart failure in acute settings

Heart Failure Phenotypes: HFrEF vs HFpEF

• BNP and NT-proBNP levels are typically higher in HFrEF than HFpEF.
• Diagnostic sensitivity is lower in HFpEF, making ‘rule-out’ less reliable in this subgroup.

Other Causes of BNP/NT-proBNP Elevation

Elevated levels may occur in the absence of heart failure due to:

• Pulmonary embolism
• Pulmonary arterial hypertension
• Atrial fibrillation
• Acute coronary syndrome
• Sepsis or critical illness

Prognostic Role in Established Heart Failure

• BNP and NT-proBNP levels correlate with disease severity and prognosis.
• Serial measurements may guide risk stratification and treatment response in chronic heart failure management.

---

Predictive Value in Other Cardiac Diseases:

• Similarly powerful predictors of major events in:
  • Myocardial infarction (MI)
  • Pulmonary arterial hypertension
  • Valvular heart disease
  • Pulmonary thromboembolism

---

Further investigations will depend on clinical circumstances

• serum cardiac troponin measurement
• plasma natriuretic peptide levels
• thyroid function tests
• arterial blood gases
• D-dimer
• stress testing (assessment for ischaemia or filling pressures)
• coronary angiography (computed tomography [CT], invasive)
• right or left heart catheterization
• lung function tests
• ventilation/perfusion lung scan
• CT pulmonary angiography
• high-resolution CT chest
• cardiopulmonary exercise testing
• cardiac magnetic resonance (CMR) imaging

When to consider early referral in the community setting (red flags)
Symptoms	• Orthopnoea • Paroxysmal nocturnal dyspnoea • Syncope • Ischaemic chest pain
Signs	• Tachycardia (heart rate >100 bpm) • Bradycardia (heart rate <40 bpm) • Hypotension (systolic BP <90 mm Hg) • Hypoxaemia • Gallop rhythm • Significant heart murmur
Investigations	• Evidence of ischaemia or infarction on 12-lead ECG • Pulmonary oedema on chest X-ray • Raised cardiac troponin level • Moderate or severe valvular heart disease on echocardiography • LVEF ≤40% • Ischaemia on stress testing