Makindo Medical Notes

Related Subjects: |Managing Chronic Heart Failure |Heart Failure and Pulmonary Oedema |Loop Diuretics |Entresto Sacubitril with Valsartan |Ivabradine |Furosemide |Angiotensin Converting Enzyme Inhibitors |Cardiac Resynchronisation Therapy (CRT) Pacemaker

💡 Key Concept: Heart failure is a clinical syndrome, not a single disease. Always identify and treat the underlying cause. Start guideline-directed medical therapy (GDMT) early and titrate to target doses to improve survival and reduce hospitalizations.

🫀 Definition

• Heart failure (HF) is a clinical syndrome in which the heart is unable to pump sufficient blood to meet the body's metabolic demands at rest or during exertion, or can only do so at the expense of elevated filling pressures.
• It is the final common pathway of various structural and functional cardiac abnormalities, not a single disease entity.
• Epidemiology: Prevalence ~2% in adults, rising to >10% in those >70 years. 5-year mortality ~50%. Leading cause of hospital admissions in elderly patients.

📊 Classification of Heart Failure

By Ejection Fraction (EF)

• HFrEF (Heart Failure with Reduced EF): EF <40%. Most evidence for pharmacological therapy. Systolic dysfunction predominates.
• HFmrEF (Heart Failure with Mildly Reduced EF): EF 41–49%. Intermediate group, treated similarly to HFrEF.
• HFpEF (Heart Failure with Preserved EF): EF ≥50%. Diastolic dysfunction predominates. Less evidence for specific therapies. More common in elderly, women, hypertension, diabetes.
• HFimpEF (Heart Failure with Improved EF): Previous EF <40% that improved to >40%. Continue HFrEF therapy as benefits persist.

By Onset

• Acute Heart Failure: Rapid onset (hours to days) or acute decompensation of chronic HF. Requires urgent/emergency treatment.
• Chronic Heart Failure: Gradual onset (weeks to months), stable symptoms. Managed with long-term GDMT.

By Anatomical Location

• Left Heart Failure: Pulmonary congestion → dyspnoea, orthopnoea, PND, pulmonary oedema. Most common.
• Right Heart Failure: Systemic venous congestion → peripheral oedema, ascites, hepatomegaly, JVP elevation. Often secondary to left HF or lung disease.
• Biventricular Failure: Both left and right heart failure features present.

⚠️ Aetiology & Causes

🔴 Common Causes (UK/Developed Countries)

• Ischaemic heart disease (40–50%): Most common cause. Post-MI ventricular remodelling, chronic CAD causing hibernating myocardium.
• Hypertension (20–30%): Chronic pressure overload → LV hypertrophy → diastolic dysfunction → systolic dysfunction.
• Valvular heart disease (10–15%):
  • Aortic stenosis (pressure overload) → LV hypertrophy.
  • Mitral regurgitation/aortic regurgitation (volume overload) → LV dilatation.
• Cardiomyopathies (10%):
  • Dilated cardiomyopathy: Idiopathic, familial/genetic (30–40%), viral myocarditis, alcohol, chemotherapy (anthracyclines, trastuzumab), peripartum, thyroid disease.
  • Hypertrophic cardiomyopathy: Genetic, causes diastolic dysfunction and outflow obstruction.
  • Restrictive cardiomyopathy: Amyloidosis, sarcoidosis, haemochromatosis, endomyocardial fibrosis.
• Arrhythmias: Atrial fibrillation (loss of atrial kick + rapid ventricular rate), tachycardia-induced cardiomyopathy (prolonged tachycardia → reversible LV dysfunction).

Less Common Causes

• Right heart failure specific: Cor pulmonale (COPD, ILD, obstructive sleep apnoea), pulmonary hypertension (idiopathic, chronic thromboembolic), pulmonary embolism, RV infarction.
• Pericardial disease: Constrictive pericarditis, cardiac tamponade (restricted filling).
• Congenital heart disease: ASD, VSD, coarctation (diagnosed in adulthood or late presentation).
• High-output states: Severe anaemia, thyrotoxicosis, sepsis, pregnancy, arteriovenous fistulae, Paget's disease, beri-beri (thiamine deficiency). Heart unable to meet excessively high metabolic demands despite normal/increased cardiac output.
• Infiltrative diseases: Cardiac amyloidosis, sarcoidosis, haemochromatosis.
• Toxins/drugs: Alcohol, cocaine, chemotherapy (doxorubicin, trastuzumab), radiation therapy.

💡 Exam Pearl: Ischaemic heart disease + hypertension = ~70–75% of HF cases in the UK. Always mention these first in exams.

🧬 Pathophysiological Mechanisms

• Pressure overload: Chronic hypertension, aortic stenosis → increased afterload → concentric LV hypertrophy (thick walls, normal cavity size) → diastolic dysfunction → eventual systolic dysfunction.
• Volume overload: Mitral/aortic regurgitation, ASD/VSD, high-output states → increased preload → eccentric LV hypertrophy (dilated cavity, relatively thin walls) → systolic dysfunction.
• Myocardial damage: MI (scar formation), myocarditis (viral, autoimmune), toxins (alcohol, chemotherapy) → loss of functional myocardium → impaired contractility.
• Restricted filling: Restrictive/hypertrophic cardiomyopathy, pericardial constriction/tamponade → impaired ventricular filling → reduced stroke volume despite preserved contractility.
• Neurohormonal activation: HF triggers compensatory mechanisms (RAAS, SNS, ADH) that initially maintain cardiac output but become maladaptive, causing fluid retention, vasoconstriction, ventricular remodelling, and disease progression.

🩺 Clinical Features

Left Heart Failure Symptoms

• Dyspnoea: Exertional dyspnoea (most common), progressing to dyspnoea at rest in severe cases.
• Orthopnoea: Breathlessness when lying flat (ask "How many pillows do you sleep on?"). Due to redistribution of fluid from legs to lungs.
• Paroxysmal nocturnal dyspnoea (PND): Sudden breathlessness waking patient from sleep, relieved by sitting upright or standing.
• Fatigue, reduced exercise tolerance: Poor tissue perfusion.
• Nocturnal cough: Pulmonary congestion.
• Pink frothy sputum: Acute pulmonary oedema (medical emergency).
• Wheeze ("cardiac asthma"): Bronchial oedema.

Right Heart Failure Symptoms

• Peripheral oedema: Ankle/leg swelling (pitting), worse at end of day, improves overnight.
• Abdominal distension: Ascites, hepatic congestion.
• Anorexia, nausea: Hepatic/bowel congestion.
• Right upper quadrant pain: Hepatic congestion (stretching of liver capsule).
• Facial/scrotal oedema: Severe fluid overload.

General Symptoms

• Weight gain (fluid retention), nocturia, confusion (elderly, poor cerebral perfusion), cachexia (cardiac cachexia in advanced HF).

Clinical Signs

• General inspection: Breathless at rest, sitting upright, cyanosis (severe), cachexia (advanced HF).
• Cardiovascular:
  • Elevated JVP (>4 cm above sternal angle) – right heart failure/fluid overload.
  • Displaced apex beat (laterally and inferiorly in dilated cardiomyopathy).
  • 3rd heart sound (S3 gallop) – rapid ventricular filling, specific for HF.
  • 4th heart sound (S4) – stiff ventricle (diastolic dysfunction).
  • Murmurs (mitral regurgitation common in dilated LV, aortic stenosis).
  • Tachycardia, narrow pulse pressure, cool peripheries (poor perfusion).
• Respiratory: Tachypnoea, bibasal fine inspiratory crackles (pulmonary oedema), pleural effusion (stony dull percussion, reduced breath sounds at bases).
• Abdominal: Ascites (shifting dullness, fluid thrill), hepatomegaly (smooth, tender, pulsatile in severe TR), hepatojugular reflux.
• Peripheral: Pitting oedema (ankles, sacrum if bed-bound), cachexia, muscle wasting.

🔍 Investigations

First-Line Investigations

• 12-lead ECG: Rarely normal in HF. Look for:
  • Previous MI (Q waves, ST/T changes).
  • LV hypertrophy (voltage criteria, strain pattern).
  • AF (loss of atrial kick worsens HF).
  • Bundle branch block (LBBB associated with HFrEF, may need CRT).
  • Normal ECG has high negative predictive value (HF unlikely).
• Chest X-ray: Look for:
  • Cardiomegaly (cardiothoracic ratio >0.5).
  • Pulmonary oedema: Alveolar oedema (bat-wing shadowing), interstitial oedema (Kerley B lines), upper lobe diversion, pleural effusions.
  • Clear lung fields do NOT exclude HF (may be chronic compensated HF or HFpEF).
• Natriuretic peptides (BNP / NT-proBNP): Released by ventricles in response to stretch/stress. Excellent negative predictive value – normal level effectively rules out HF.
  • BNP levels:
    • <100 pg/mL: HF unlikely (high negative predictive value).
    • 100–400 pg/mL: Consider HF, perform echocardiography.
    • >400 pg/mL: HF likely, urgent echocardiography (within 2 weeks).
  • NT-proBNP levels (age-adjusted):
    • <50 years: <300 pg/mL normal.
    • 50–75 years: <900 pg/mL normal.
    • >75 years: <1800 pg/mL normal.
  • Causes of elevated BNP/NT-proBNP (besides HF): ACS, pulmonary embolism, pulmonary hypertension, CKD (reduced clearance), severe sepsis, LV hypertrophy, AF, advanced age.
  • Factors lowering BNP: Obesity (levels may be falsely low), flash pulmonary oedema.
  • Correlation with severity: Higher levels = worse NYHA class, poorer prognosis. Useful for monitoring treatment response (serial measurements).

Essential Investigations

• Transthoracic echocardiography (TTE): Gold standard for diagnosis and classification.
  • Assess LV systolic function (ejection fraction, regional wall motion abnormalities).
  • Assess diastolic function (E/A ratio, E/e' ratio, LA size).
  • Valvular pathology (stenosis, regurgitation).
  • Right ventricular function and pulmonary artery pressure.
  • Pericardial effusion, tamponade.
  • All patients with suspected HF must have echocardiography to confirm diagnosis and guide treatment.
• Blood tests:
  • FBC: Anaemia (worsens HF, assess for cause), leucocytosis (infection as precipitant).
  • U&E: Baseline renal function (many HF drugs affect kidneys), hypokalaemia/hyperkalaemia (diuretics, RAAS inhibitors), hyponatraemia (poor prognosis marker).
  • LFTs: Hepatic congestion (↑transaminases, ↑bilirubin), baseline before amiodarone/statins.
  • TFTs: Hypo/hyperthyroidism can cause or worsen HF.
  • HbA1c: Diabetes is major risk factor and comorbidity.
  • Lipid profile: Ischaemic heart disease risk stratification.
  • Troponin: If ACS suspected as precipitant.
  • CRP/ESR: Infection, inflammation (myocarditis).
• Urine dipstick: Proteinuria (CKD, diabetes), infection.

Additional Investigations (Selected Cases)

• Coronary angiography: If ischaemic aetiology suspected (angina, previous MI, regional wall motion abnormalities on echo). Revascularization may improve function (viable myocardium).
• Cardiac MRI: Detailed assessment of structure/function, tissue characterization (fibrosis, infiltration, inflammation). Useful in cardiomyopathies, myocarditis, amyloidosis.
• Cardiopulmonary exercise testing (CPET): Objective assessment of functional capacity (peak VO₂). Used for heart transplant listing, prognosis.
• 24-hour Holter monitor: Detect paroxysmal AF, ventricular arrhythmias.
• Endomyocardial biopsy: Rare, for suspected infiltrative/inflammatory cardiomyopathy undiagnosed by non-invasive means.

🚨 NYHA Functional Classification

• Class I: No limitation. Ordinary physical activity does not cause symptoms.
• Class II: Slight limitation. Comfortable at rest, ordinary activity causes symptoms.
• Class III: Marked limitation. Comfortable at rest, less than ordinary activity causes symptoms.
• Class IV: Severe limitation. Symptoms at rest, any activity worsens symptoms.
• Clinical use: Guides treatment intensity, prognosis, device therapy decisions. Document at each visit.

📊 Left vs Right Heart Failure Comparison

💊 Management of HFrEF (EF <40%)

⚡ GDMT (Guideline-Directed Medical Therapy) = "Fantastic Four": ACEi/ARNI + Beta-blocker + MRA + SGLT2i. Start early, titrate to target doses. These drugs reduce mortality by up to 60% when used in combination.

First-Line Pharmacotherapy (Start All Four ASAP)

• 🧩 ACE Inhibitors (ACEi):
  • Examples: Ramipril, lisinopril, enalapril.
  • Mechanism: Block RAAS → reduce afterload, preload, prevent adverse remodelling.
  • Mortality benefit: 20–30% reduction.
  • Dosing: Start low (ramipril 1.25 mg OD), titrate every 2–4 weeks to target (ramipril 10 mg OD).
  • Monitoring: U&E and renal function at baseline, 1–2 weeks after initiation/dose increase. Acceptable: creatinine rise <30%, K⁺ <5.5 mmol/L.
  • Side effects: Dry cough (10–15%, switch to ARB), hyperkalaemia, renal impairment, first-dose hypotension, angioedema (rare, 0.1–0.2%).
  • Contraindications: Pregnancy, bilateral renal artery stenosis, previous angioedema.
• 🔒 ARBs (Angiotensin Receptor Blockers):
  • Examples: Losartan, valsartan, candesartan.
  • Use: Alternative if ACEi-intolerant (cough, angioedema). Similar efficacy to ACEi.
  • Dosing: Candesartan 4 mg OD → target 32 mg OD.
  • Advantage: No cough (does not affect bradykinin).
• ⚡ ARNIs (Angiotensin Receptor-Neprilysin Inhibitors):
  • Example: Sacubitril/valsartan (Entresto).
  • Mechanism: ARB + neprilysin inhibitor (increases natriuretic peptides → vasodilation, natriuresis).
  • Indication: NYHA class II–IV HFrEF, replace ACEi/ARB if ongoing symptoms despite treatment.
  • Mortality benefit: 20% reduction vs enalapril (PARADIGM-HF trial).
  • Dosing: Start 24/26 mg or 49/51 mg BD → target 97/103 mg BD.
  • CRITICAL: 36-hour washout from ACEi before starting (angioedema risk if overlap).
  • Monitoring: BP, U&E, renal function. Avoid if systolic BP <100 mmHg.
  • Side effects: Hypotension, hyperkalaemia, renal impairment, angioedema (lower risk than ACEi).
• 🛡️ Beta-Blockers:
  • HF-licensed drugs ONLY: Bisoprolol, carvedilol, metoprolol succinate (NOT metoprolol tartrate).
  • Mechanism: Block sympathetic overdrive → reduce heart rate, myocardial oxygen demand, prevent arrhythmias, improve remodelling.
  • Mortality benefit: 30–35% reduction.
  • Dosing: Bisoprolol 1.25 mg OD → target 10 mg OD. Double dose every 2–4 weeks if tolerated.
  • Start ONLY when patient stable (not during acute decompensation). Initiate in hospital or within days of discharge after acute HF.
  • Target heart rate: 50–60 bpm at rest.
  • Monitoring: Heart rate, BP, signs of worsening HF. Temporary worsening in first weeks is common (persevere unless severe).
  • Side effects: Bradycardia, hypotension, fatigue, worsening HF initially, bronchospasm (use with caution in asthma/COPD).
  • Contraindications: Severe bradycardia, heart block, acute decompensated HF, severe asthma.
• 🌀 Mineralocorticoid Receptor Antagonists (MRAs):
  • Examples: Spironolactone (causes gynaecomastia), eplerenone (selective, less gynaecomastia).
  • Mechanism: Block aldosterone → reduce sodium/water retention, prevent myocardial fibrosis.
  • Indication: NYHA class II–IV with EF ≤35%, or post-MI with EF <40% and HF symptoms.
  • Mortality benefit: 30% reduction (RALES trial).
  • Dosing: Spironolactone 12.5–25 mg OD → target 25–50 mg OD.
  • Monitoring: K⁺ and renal function at baseline, 1 week, 4 weeks, then 3-monthly. Stop if K⁺ >5.5 mmol/L or creatinine >221 µmol/L.
  • Side effects: Hyperkalaemia (5–10% risk, especially with ACEi/ARNI), renal impairment, gynaecomastia (spironolactone 10%).
  • Contraindications: K⁺ >5.0 mmol/L, severe renal impairment (eGFR <30).
• 💧 SGLT2 Inhibitors (Sodium-Glucose Co-Transporter-2 Inhibitors):
  • Examples: Dapagliflozin 10 mg OD, empagliflozin 10 mg OD.
  • Mechanism: Inhibit glucose reabsorption in proximal tubule → glycosuria, natriuresis, osmotic diuresis. Cardiac benefits independent of glucose-lowering (exact mechanism unclear: improved energetics, reduced inflammation, haemodynamic effects).
  • Indication: ALL patients with HFrEF, regardless of diabetes status (DAPA-HF, EMPEROR-Reduced trials).
  • Benefits: 30% reduction in HF hospitalization, 13–18% reduction in cardiovascular death. Also beneficial in HFpEF.
  • Dosing: Dapagliflozin 10 mg OD (fixed dose, no titration needed).
  • Monitoring: eGFR (avoid if <20), volume status, genital infections.
  • Side effects: Genital mycotic infections (3–5%, more in women), UTIs, volume depletion (rare), euglycaemic DKA (very rare, avoid if T1DM).
  • Advantages: Simple dosing, low risk of hypotension/hyperkalaemia, no need for slow titration.

Additional Therapies (For Specific Indications)

• ❤️‍🔥 Ivabradine:
  • Mechanism: Selective If channel inhibitor → slows heart rate without negative inotropic effect.
  • Indication: NYHA class II–IV in sinus rhythm with heart rate ≥70 bpm despite maximum tolerated beta-blocker (or beta-blocker contraindicated).
  • Benefit: 18% reduction in HF hospitalization (SHIFT trial).
  • Dosing: 5 mg BD → target 7.5 mg BD. Aim for heart rate 50–60 bpm.
  • Side effects: Visual disturbances (phosphenes – seeing flashes), bradycardia.
  • Contraindications: AF (ineffective), severe bradycardia/heart block.
• 💦 Loop Diuretics:
  • Examples: Furosemide, bumetanide, torsemide.
  • Indication: Fluid overload, congestion (dyspnoea, oedema). For symptom relief ONLY – no mortality benefit.
  • Dosing: Furosemide 20–40 mg OD/BD initially, titrate to symptoms and daily weights. Bumetanide 1 mg = furosemide 40 mg (more reliable oral absorption).
  • Monitoring: Daily weights (aim for 0.5–1 kg loss/day in acute setting), U&E (risk of hypokalaemia, hyponatraemia, renal impairment).
  • Diuretic resistance: If poor response, increase dose, switch to IV, add thiazide (metolazone, bendroflumethiazide), or combine with acetazolamide.
  • Side effects: Hypokalaemia, hyponatraemia, hypovolaemia, renal impairment, ototoxicity (high doses), gout.
• 💛 Hydralazine + Nitrates: