Orthopnoea and paroxysmal nocturnal dyspnoea

Orthopnoea is breathlessness on lying flat that is relieved within minutes by sitting or standing upright; it is quantified by the number of pillows needed (two pillow, three pillow orthopnoea) or by the angle of sleep. Paroxysmal nocturnal dyspnoea is sudden breathlessness, cough or wheeze that wakes the patient 1 to 3 hours after lying down and that eases over 10 to 30 minutes after sitting up, often with the patient rushing to an open window.

Both arise from pulmonary venous congestion on recumbency and are classic features of left heart failure, but also have respiratory, abdominal, neuromuscular and sleep related causes.

Clinical relevance. Orthopnoea has about 90% specificity for heart failure with raised filling pressure and predicts hospital admission and death; paroxysmal nocturnal dyspnoea is also specific but less sensitive. Worsening pillow count over days is an early sign of decompensation and a trigger to adjust diuretics before admission is needed. Other causes (diaphragm paralysis, obesity, chronic lung disease) are easily missed. Classification.

• Orthopnoea of cardiac origin: left ventricular failure (reduced and preserved ejection fraction), valve disease (mitral stenosis, mitral and aortic regurgitation, aortic stenosis), constrictive pericarditis, restrictive cardiomyopathy, arrhythmia, shunts.
• Pulmonary and airway: chronic obstructive pulmonary disease, asthma (nocturnal), interstitial lung disease, large pleural effusion, massive ascites or abdominal distension, severe kyphoscoliosis, bronchiectasis, upper airway obstruction.
• Neuromuscular: bilateral diaphragm paralysis (orthopnoea without paroxysmal nocturnal dyspnoea, with paradoxical abdominal movement when supine), motor neurone disease, myasthenia gravis, Guillain-Barre syndrome, muscular dystrophy, spinal cord injury.
• Other: obesity, pregnancy, gastro-oesophageal reflux with aspiration, obstructive sleep apnoea, anxiety and panic, anaemia.

Related terms. Platypnoea is breathlessness on sitting or standing that eases when lying (hepatopulmonary syndrome, patent foramen ovale with right to left shunt, pulmonary arteriovenous malformation, diaphragm paralysis in some, postpneumonectomy). Trepopnoea is breathlessness lying on one side (unilateral lung disease, large pleural effusion, ventricular dysfunction, mediastinal mass). Cardiac asthma is wheeze from bronchial wall oedema in left heart failure.

Mechanism. Lying flat redistributes 300 to 500 mL of blood from the legs and splanchnic bed to the thorax and raises left atrial and pulmonary venous pressure; fluid reabsorbed from dependent oedema at night adds to preload; recumbency raises diaphragm position and lowers lung volume; sleep lowers adrenergic tone, ventilatory drive and cough sensitivity.

History.

• Orthopnoea: number of pillows, change over time, sleeping in a chair, onset time after lying, relief with sitting, relation to meals; compare with baseline.
• Paroxysmal nocturnal dyspnoea: timing after sleep onset, duration, cough, wheeze, pink frothy sputum, need to open a window; distinguish from panic attacks (shorter, no orthopnoea), asthma and reflux.
• Exertional breathlessness (New York Heart Association class), ankle swelling, weight gain (over 2 kg in 3 days), fatigue, nocturia, abdominal bloating, early satiety, palpitations, chest pain, syncope.
• Cardiac history: hypertension, coronary disease, valve disease, rheumatic fever, arrhythmia, cardiomyopathy, congenital disease, previous heart failure, alcohol, chemotherapy (anthracyclines, trastuzumab), radiotherapy.
• Respiratory history: smoking, chronic cough, wheeze, asthma, occupational exposure, tuberculosis, interstitial lung disease.
• Neuromuscular history: dysphagia, weakness, speech or swallowing change, fasciculations.
• Abdominal history: ascites, liver disease, obesity, pregnancy.
• Drugs: NSAIDs, pioglitazone, calcium channel blockers (non dihydropyridine), beta blockers (stopped or started), steroids, adherence to diuretics, salt and fluid intake, recent infection.
• Sleep: snoring, witnessed apnoeas, daytime sleepiness, restless sleep, morning headache.

Examination.

• Vital signs, respiratory rate, oxygen saturation, blood pressure, pulse (rhythm, pulsus alternans), temperature, weight.
• Work of breathing, ability to speak in sentences, accessory muscle use, abdominal paradox lying flat.
• Jugular venous pressure (raised, hepatojugular reflux), apex beat (displaced), third heart sound (gallop), murmurs (mitral stenosis, mitral regurgitation, aortic stenosis or regurgitation), loud pulmonary second sound.
• Chest: bilateral basal crackles (do not rely on them in chronic failure), wheeze, dullness (effusion), reduced breath sounds.
• Abdomen: hepatomegaly, ascites; legs: pitting oedema, sacral oedema; cold peripheries.
• Neurological: respiratory muscle weakness, single breath count, bulbar signs.
• Obesity, neck circumference, Mallampati score.

Red flags.

• Breathlessness at rest, saturation under 90%, respiratory rate over 25, inability to speak in sentences.
• Pink frothy sputum, cold clammy skin, hypotension (systolic under 90 mmHg), confusion, syncope.
• Chest pain or ECG ischaemia; new arrhythmia; heart rate over 130.
• New murmur with fever (endocarditis); acute severe mitral regurgitation.
• Orthopnoea with progressive neuromuscular weakness, bulbar symptoms or vital capacity under 1 litre (or under 20 mL/kg).
• Sudden onset orthopnoea with pleuritic pain or leg swelling (pulmonary embolism).
• Haemoptysis, weight loss, or a mediastinal mass.

Cardiac.

• Heart failure with reduced ejection fraction: ischaemic, hypertensive, dilated, alcoholic, peripartum, chemotherapy induced, myocarditis, Chagas disease, tachycardia induced, HIV related cardiomyopathy.
• Heart failure with preserved ejection fraction: hypertension, diabetes, obesity, atrial fibrillation, ageing, hypertrophic and restrictive cardiomyopathy, cardiac amyloidosis.
• Valve disease: rheumatic mitral stenosis and regurgitation, aortic stenosis, aortic regurgitation, prosthetic valve dysfunction, endocarditis.
• Pericardial: constrictive pericarditis (tuberculous in endemic areas), tamponade.
• Arrhythmia: atrial fibrillation with fast rate, ventricular tachycardia, bradycardia.
• Congenital: shunts, Eisenmenger syndrome.
• High output states: anaemia, thyrotoxicosis, beriberi, arteriovenous fistula, pregnancy, Paget disease.

Pulmonary and airway. Chronic obstructive pulmonary disease, asthma, interstitial lung disease, bronchiectasis, pleural effusion, pneumonia, lung cancer, pulmonary hypertension, chronic thromboembolic disease, obesity hypoventilation syndrome, upper airway obstruction, goitre or mediastinal mass.

Abdominal and chest wall. Massive ascites, large abdominal mass, severe obesity, pregnancy, kyphoscoliosis, ankylosing spondylitis.

Neuromuscular. Bilateral diaphragm paralysis (idiopathic, phrenic neuropathy, cardiac surgery, neuralgic amyotrophy, trauma), motor neurone disease, myasthenia gravis, Guillain-Barre syndrome, Pompe disease and muscular dystrophy, spinal cord injury.

Sleep and functional. Obstructive sleep apnoea, central sleep apnoea and Cheyne-Stokes respiration (with heart failure), gastro-oesophageal reflux with nocturnal aspiration, anxiety and panic attacks, nocturnal asthma.

1. Treat first if unstable; otherwise take a full history and examination, with the pillow count and weight as baseline for comparison at follow up.
2. Natriuretic peptides: NT-proBNP under 300 pg/mL (BNP under 100 pg/mL) rules out acute heart failure. For chronic non acute presentation NT-proBNP under 125 pg/mL (BNP under 35 pg/mL) makes heart failure unlikely. Levels rise with age, atrial fibrillation and kidney disease, and fall in obesity and with sacubitril-valsartan (use NT-proBNP rather than BNP on sacubitril-valsartan).
3. 12 lead ECG (ischaemia, atrial fibrillation, left ventricular hypertrophy, bundle branch block, low voltage) and chest radiograph (cardiomegaly, upper lobe venous diversion, Kerley B lines, effusions, hyperinflation, diaphragm elevation).
4. Echocardiography: ejection fraction, diastolic function (E/e' ratio, left atrial volume), valve disease, pulmonary pressure, pericardial disease, right ventricular function. Cardiac MRI for cardiomyopathy, myocarditis and infiltrative disease; coronary angiography or CT coronary angiography for ischaemia.
5. Blood tests: full blood count, urea, creatinine, electrolytes, liver function tests, albumin, glucose or HbA1c, thyroid stimulating hormone, troponin, lipids, HIV test, and arterial or venous blood gas.
6. Iron studies: ferritin under 100 micrograms/L, or 100 to 299 with transferrin saturation under 20%, defines iron deficiency in heart failure.
7. Lung ultrasound for B lines (three or more in two zones bilaterally supports pulmonary oedema), pleural effusion and diaphragm movement.
8. Pulmonary function: spirometry and lung volumes (restriction, obstruction). Lying and sitting vital capacity (a fall of over 20% when supine suggests diaphragm weakness). Maximal inspiratory and sniff nasal pressures. Diaphragm ultrasound (thickening under 20% on inspiration, or excursion under 1 cm).
9. Sleep study when snoring, obesity or heart failure with suspected central apnoea.
10. Ambulatory ECG, exercise testing or cardiopulmonary exercise testing when cause is unclear; right heart catheterisation for pulmonary hypertension.
11. Gastroscopy or pH monitoring if reflux is a candidate cause.

Limits. Orthopnoea is subjective and may be learned and avoided by sleeping in a chair. Absent crackles do not exclude heart failure in chronic disease. Natriuretic peptides are raised by many non cardiac conditions, including pulmonary embolism, sepsis and kidney failure. Echocardiography at rest can be normal early in heart failure with preserved ejection fraction.

Acute pulmonary oedema or decompensated heart failure.

• Sit upright with legs dependent. Apply monitoring and high flow oxygen only if saturation is under 90% (target 94% to 98%, avoid hyperoxia). Establish intravenous access.
• Intravenous loop diuretic: furosemide 40 mg (20 to 40 mg for diuretic naive patients; at least the usual oral daily dose given intravenously for chronic users, often 40 to 80 mg), repeated in 1 to 2 hours if urine output under 100 to 150 mL/hour.
• Then give an infusion of 5 to 40 mg/hour if needed. Add metolazone 2.5 to 5 mg orally (or bendroflumethiazide 5 mg) for resistant oedema, with potassium and sodium monitoring. Target net negative balance 1 to 2 litres/day.
• Vasodilator when systolic pressure is over 110 mmHg: glyceryl trinitrate sublingual 400 micrograms (or buccal 2 to 5 mg) then infusion 10 to 200 micrograms/minute.
• Non invasive ventilation or continuous positive airway pressure 5 to 10 cmH2O for respiratory distress, respiratory rate over 25 or saturation under 90% despite oxygen.
• Opiates are not routine (morphine 2.5 to 5 mg only for severe distress in exceptional cases, as it is associated with higher intubation rates).
• Treat the precipitant: acute coronary syndrome (aspirin 300 mg, antithrombotic therapy, coronary angiography), arrhythmia (rate control or cardioversion), infection (antibiotics), uncontrolled hypertension, anaemia, kidney failure, drug non adherence, thyroid disease, pulmonary embolism, valve emergency (surgery).
• Cardiogenic shock: inotropes (dobutamine 2.5 to 10 micrograms/kg/minute) or vasopressors (noradrenaline 0.05 to 0.5 micrograms/kg/minute), mechanical circulatory support; urgent cardiology and critical care.
• Dialysis or ultrafiltration for diuretic refractory overload.

Chronic heart failure with reduced ejection fraction (40% or under). Start all four classes together or in rapid sequence.

• ACE inhibitor: ramipril 1.25 to 2.5 mg twice daily, doubling every 1 to 2 weeks to 5 mg twice daily or 10 mg daily; lisinopril 2.5 to 5 mg daily to 20 to 35 mg daily; perindopril 2 mg daily to 8 mg daily.
• Replace the ACE inhibitor with sacubitril-valsartan 24/26 mg twice daily, increasing every 2 to 4 weeks to 97/103 mg twice daily (36 hour washout from an ACE inhibitor; avoid with angioedema).
• Angiotensin receptor blocker (candesartan 4 mg to 32 mg daily) if ACE inhibitor is not tolerated. Check creatinine and potassium at 1 to 2 weeks.
• Beta blocker started when euvolaemic: bisoprolol 1.25 mg daily increasing every 2 weeks to 10 mg daily, carvedilol 3.125 mg twice daily to 25 mg twice daily (50 mg twice daily if over 85 kg), nebivolol 1.25 mg daily to 10 mg daily.
• Mineralocorticoid receptor antagonist: spironolactone 25 mg daily (12.5 mg if eGFR 30 to 50) or eplerenone 25 mg daily increasing to 50 mg daily. Check potassium and creatinine at 1 week, 4 weeks, then every 3 to 6 months; stop if potassium over 5.5 mmol/L.
• Sodium glucose co-transporter 2 inhibitor: dapagliflozin 10 mg daily or empagliflozin 10 mg daily (eGFR 20 or more). Advise on genital hygiene, sick day rules and ketoacidosis warning.
• Diuretic for congestion at the lowest dose that keeps euvolaemia: furosemide 20 to 80 mg daily, bumetanide 1 to 5 mg daily, or torasemide 10 to 40 mg daily, with a daily weight and a flexible dose plan.
• Add ivabradine 5 mg twice daily (maximum 7.5 mg twice daily) in sinus rhythm with rate 70 beats/minute or more on maximum beta blocker.
• Add hydralazine 25 mg three times daily with isosorbide dinitrate 20 mg three times daily if intolerant of renin angiotensin drugs (and in people of African ancestry added to therapy).
• Digoxin 62.5 to 250 micrograms daily for atrial fibrillation or persistent symptoms. Vericiguat 2.5 mg increasing to 10 mg daily after worsening events.
• Intravenous iron (ferric carboxymaltose 500 to 1,000 mg, dose by weight and haemoglobin) for iron deficiency.
• Devices: implantable cardioverter defibrillator for ejection fraction 35% or less after at least 3 months of optimal therapy with expected survival over 1 year; cardiac resynchronisation for QRS 150 ms or more with left bundle branch block and ejection fraction 35% or less.

Heart failure with preserved ejection fraction. Diuretics for congestion; dapagliflozin 10 mg or empagliflozin 10 mg daily; treat hypertension, atrial fibrillation (rate control, anticoagulation), obesity, diabetes, sleep apnoea and coronary disease; spironolactone 25 mg daily may reduce admissions; sacubitril-valsartan in selected patients (lower ejection fraction range); exercise training; semaglutide in obesity related disease.

Valve and pericardial disease. Mitral stenosis: diuretics, rate control (beta blocker or diltiazem), anticoagulation with warfarin (INR 2 to 3), balloon valvotomy or surgery. Aortic stenosis: valve replacement for symptomatic disease. Acute mitral or aortic regurgitation: vasodilators and urgent surgery.

Constrictive pericarditis: diuretics and pericardiectomy.

Tuberculous pericarditis needs prednisolone and antituberculous treatment: isoniazid 5 mg/kg to a maximum of 300 mg, rifampicin 10 mg/kg to a maximum of 600 mg, pyrazinamide 25 mg/kg to a maximum of 2 g, and ethambutol 15 mg/kg for 2 months. Then give isoniazid and rifampicin for 4 months, with pyridoxine.

Non cardiac causes.

• Chronic obstructive pulmonary disease and asthma: inhaled bronchodilators and corticosteroids, treat nocturnal symptoms (long acting bronchodilator at night), pulmonary rehabilitation.
• Diaphragm paralysis and neuromuscular disease: non invasive ventilation (nocturnal bilevel with inspiratory pressure 10 to 20 cmH2O and expiratory 4 to 6 cmH2O), cough assist. Diaphragm plication for unilateral symptomatic paralysis. Treat the cause (immunotherapy for myasthenia, riluzole 50 mg twice daily for motor neurone disease).
• Obesity hypoventilation and sleep apnoea: weight loss, continuous positive airway pressure or bilevel support, and avoid sedatives.
• Large pleural effusion: therapeutic drainage; ascites: paracentesis with albumin 8 g for each litre removed over 5 litres; pregnancy: reassurance and sleeping propped.
• Reflux: head of bed raised, omeprazole 20 to 40 mg daily, avoid late meals.
• Panic attacks: explanation and breathing retraining; cognitive therapy.

Self management for heart failure. Daily weights (call for gain over 2 kg in 3 days), fluid restriction 1.5 to 2 litres only in advanced or hyponatraemic disease, salt moderation, no NSAIDs, vaccination (influenza, pneumococcus, COVID-19), exercise rehabilitation, stop smoking, limit alcohol, flexible diuretic plan.

Monitoring. Weight, pillow count, symptoms, blood pressure, heart rate; urea, creatinine, potassium and sodium at 1 to 2 weeks after each change, then every 3 to 6 months; natriuretic peptide to guide in selected cases; echocardiography 3 to 6 months after optimal therapy and with any clinical change; ECG; device checks.

Referral and escalation. Cardiology and heart failure nurse specialist for all new heart failure, advanced therapy, devices and valve disease; respiratory or sleep medicine for pulmonary and sleep disorders; neurology for neuromuscular disease; palliative care for end stage disease.

Admission. Breathlessness at rest, hypoxia, haemodynamic instability, new or rapid arrhythmia, ischaemia, kidney injury, failure of oral diuretic treatment, or severe comorbidity.

Safety netting. Return urgently for breathlessness at rest, pink frothy sputum, chest pain, fainting, a rapid heartbeat, passing little urine, or weight gain over 2 kg in 3 days with worsening swelling or pillow count.

Special groups. Pregnancy: peripartum cardiomyopathy and mitral stenosis worsen in the third trimester and after delivery. Avoid ACE inhibitors, angiotensin receptor blockers and spironolactone (use hydralazine with nitrate, beta blocker, furosemide). In peripartum cardiomyopathy give bromocriptine 2.5 mg twice daily for 1 week then 2.5 mg daily for 6 weeks, with anticoagulation.

Older adults: atypical symptoms, HFpEF predominates, careful diuretic dosing. Children: congenital shunts and cardiomyopathy. Endemic regions: rheumatic heart disease, Chagas disease, tuberculous pericarditis, HIV cardiomyopathy, hypertensive heart disease, anaemia and peripartum cardiomyopathy account for most cases.