Heart Failure

Heart failure is a complex clinical syndrome with typical symptoms and signs that generally occur on exertion, but can also occur at rest (particularly when recumbent)
Typical symptoms:
- Dyspnoea(cardinal symptom)
- Orthopnoea
- paroxysmal nocturnal dyspnoea
- exertional dyspnoea
- bendopnoea
- palpitations.
Typical signs
- related to cardiac dysfunction and strain
  - tachycardia
  - third heart sound
  - murmurs
  - displaced apex beat
- reduced end-organ perfusion
- congestion
  - abnormal cardiac filling resulting in high venous pressure
    - elevated JVP
  - hepatic enlargement and tenderness
  - peripheral oedema
  - pulmonary crackles
  - pleural effusions
  - ascites

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 (shortness of breath 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

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 diagnostic criteria
HFrEF	HFpEF (Preserved Ejection Fraction)
Symptoms ± signs of heart failure andLVEF <50%	Symptoms ± signs of heart failure. AND LVEF ≥50%. AND Objective evidence of: – Relevant structural heart disease – LV hypertrophy – left atrial enlargement AND / OR Diastolic dysfunction, with high filling pressure demonstrated by any of the following: – invasive means (cardiac catheterization= pulmonary capillary wedge pressure (PCWP) of more than or equal to 15 mm Hg or LV end-diastolic pressure of more than 16 mm Hg) – echocardiography – biomarker (elevated BNP or NT proBNP) – exercise testing (invasive or echocardiography)

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

Terminology

Asymptomatic left ventricular dysfunction

refers to reduced LVEF (<50%) with no current or prior clinical evidence of heart failure. Its importance lies in being a strong risk factor for the development of heart failure.

New onset or de novo heart failure

refers to the first presentation and diagnosis of heart failure in a patient. The history of symptoms may be short (hours to days) or long (weeks to months). It follows that these patients have not previously received heart failure treatment.

Chronic heart failure

refers to patients with diagnosed heart failure for a period of time (arbitrarily defined as a minimum of 3 months). It follows that these patients have received some heart failure treatment.

Acute heart failure

can take many forms and represents a heterogeneous group. It refers to the acute onset or significant worsening of symptoms of heart failure sufficient to warrant treatment intervention. Specific subgroups of acute heart failure are described below:

Acute (cardiogenic) pulmonary oedema (APO)
- A medical emergency characterised by the acute (often within minutes or hours) development of pulmonary oedema as the dominant clinical feature of left heart failure with redistribution of fluid into the pulmonary interstitium and then alveolar flooding.
- APO results in the rapid development of respiratory failure and potentially respiratory arrest and death without intervention.

Cardiogenic shock
- A medical emergency with a particularly poor prognosis.
- Cardiogenic shock is typically characterised by the acute development of
  - reduced cardiac output (cardiac index <2.2 L/min/m2) and
  - hypotension (systolic blood pressure [BP] <90 mm Hg) in the setting of heart failure (PCWP > 18 mm Hg) to the point where
  - end-organ perfusion is compromised.
- Without intervention, multiorgan failure and death ensues.
- Cardiogenic shock most commonly results from a
  - large acute myocardial functional insult (e.g., acute myocardial infarction (MI) or
  - acute fulminant myocarditis) or
  - catastrophic cardiac structural insult (e.g., acute torrential valvular regurgitation).
- Cardiogenic shock is increasingly seen in the older comorbid population as an end-stage phenomenon in the chronic heart failure (CHF) illness trajectory, where it typically has a more subacute onset

Acute decompensated heart failure (ADHF)
- The most common form of acute heart failure in Australia is an acute deterioration (decompensation) in a previously stable patient with CHF.
- The precipitants for decompensation are multiple and varied, ranging from patient factors, disease state factors and comorbidities.
- The precipitants of decompensation often require attention in their own right, concurrent with management of the heart failure.
- While ADHF can present acutely, it more typically presents with a subacute history of several weeks of gradual deterioration with symptoms and signs of congestion.

Right heart failure
- refers to solitary or predominant failure of the right heart.
- Rare causes
  - RV infarction
  - isolated tricuspid valve pathology
  - right heart pressure overload

Right heart pressure overload

The right heart is a low-pressure system, and consequently it is particularly sensitive to high afterload (pulmonary hypertension).
Pulmonary hypertension is a consequence of many prevalent chronic diseases in Australian society;
- e.g., HFrEF
- HFpEF
- Hypertension
- left-sided valvular heart disease
- atrial fibrillation (AF)
- obesity
- chronic lung disease
- sleep apnoea
- chronic renal failure
- pulmonary thromboemboli
Unfortunately, right heart failure is an advanced illness phenomenon with a particularly poor prognosis

Pathophysiology

Heart Failure with Reduced Ejection Fraction
- Patients with HFrEF have reduced LV systolic function due to a number of underlying causes
- Reduced systolic function will reduce cardiac output, which has multiple negative consequences:
  - reduced end-organ perfusion;
  - activation of neurohormonal (e.g., renin-angiontensin-aldosterone system, sympathetic nervous system), and inflammatory systems;
  - cardiac remodelling (LV dilatation, myocyte hypertrophy, and myocardial fibrosis);
  - worsening cardiac function.

Heart Failure with Preserved Ejection Fraction
- The pathophysiology of HFpEF is less well defined. Its wide acceptance as a true syndromic entity remained under question until relatively recently [[30]]. It is accepted that this condition is a major source of heart failure morbidity, seen in typically comorbid and older patients.
- Specifically, the entity is more prevalent in older, female patients with a history of hypertension as well as obesity, diabetes, and AF.
- Prevailing current pathophysiological theories include:
  - a causal role for comorbidities and consequent coronary microvascular inflammation leading to myocyte hypertrophy and reduced cyclic guanosine monophosphate, resulting in hypophosphorylation of titin (reducing myocardial relaxation) and myocardial fibrosis (reducing myocardial compliance)
  - central arterial stiffening, resulting in a rapidly reflected arterial pulse wave, thereby increasing LV afterload
  - skeletal muscle oxygen delivery and extraction abnormalities
  - subtle abnormalities in contractile and chronotropic reserve
- This ongoing pathophysiological uncertainty has undoubtedly contributed to the lack of treatment success for this common condition

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
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

Orthopnoea
paroxysmal nocturnal dyspnoea
associated symptoms such as chest pain, palpitations, dizziness, syncope, swollen ankles, and abdominal bloating

Symptoms and signs of heart failure.

Symptoms and signs of heart failure
More typical symptoms	More specific signs
Dyspnoea (usually with exertion) Orthopnoea ((shortness of breath) that occurs when a person lies flat.) Paroxysmal nocturnal dyspnoea (sudden, severe shortness of breath that awakens a person from sleep, usually occurring several hours after the onset of sleep) 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 (shortness of breath 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

Exam

Cardiac Auscultation – Tachycardia, S3 Gallup Rhythm, Cardiac Murmur
Fluid status exam – Jugular Venous Distention, Hepatojugular Reflex, Peripheral Edema
Body weight (trend in recent weights)
Peripheral Vascular Exam – Decreased pulses or bruits, Pulsus Paradoxus (>10 mm Hg Blood Pressure drop with inspiration)
Airway Exam (includes nose and sinus exam) – stridor. Drooling, Trismus, Peritonsillar Abscess, Muffled voice
Respiratory Exam – Increased AP Chest diameter, Wheezing, Rales, Accessory Muscle use (Neck, chest, Abdomen)
Neurologic Exam- Cranial Nerve deficit such as Ptosis, Diplopia, Dysarthria (Myasthenia Gravis), Symmetric leg weakness and Deep Tendon Reflex loss (Guillain Barre)
Musculoskeletal Exam – Severe kyphoscoliosis, Pectus Excavatum, Ankylosing Spondylitis
Skin Exam- Cyanosis or Pallor, Digital Clubbing
Psychomotor exam, Anxiety

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 Cut-offs:

Precise cut-offs vary between trials.
Influenced by individual patient characteristics (e.g., age, weight, renal function).
Pragmatic guide: BNP < 100 ng/L and NT-proBNP < 300 ng/L for rule-out.

Comparison in Heart Failure Types:

Levels generally lower in HFpEF (Heart Failure with preserved Ejection Fraction) than in HFrEF (Heart Failure with reduced Ejection Fraction).
‘Rule-out’ reliability of BNP and NT-proBNP weaker in HFpEF compared to HFrEF.

Elevation in Other Cardiovascular Conditions:

Elevated in conditions like pulmonary thromboembolism, pulmonary arterial hypertension, atrial fibrillation (AF), and acute coronary syndromes.

Prognostic Use in Heart Failure:

Can be used for prognostic stratification in patients with an established heart failure diagnosis.

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