GC084 Shortness Of Breath On Exertion
Dyspnea triggered by physical activity, indicating that the cardiovascular or respiratory system cannot adequately meet the increased oxygen demands of exertion.
Shortness of Breath on Exertion: Heart Failure
This lecture by Professor Kai-Hang Yiu (Cardiology Division, HKU) is the cornerstone GC session on Heart Failure (HF) presented through the lens of the most common cardiac symptom it produces: shortness of breath on exertion (SOBOE). The lecture systematically answers six questions [1]:
- What is Heart Failure?
- How to approach SOB on exertion?
- How to diagnose HF?
- How to stage HF?
- What are the causes of HF?
- How to treat HF?
Big idea: SOB on exertion is a very sensitive but non-specific symptom. When the cause is cardiac, the dominant pathology is heart failure — a clinical syndrome (not a single disease) where the heart cannot pump blood at a rate commensurate with metabolic demands. The lecture walks you from first principles of physiology (Frank-Starling law, double circulation, Starling forces) through diagnosis (Framingham/Boston criteria, BNP, echo), staging (NYHA/ACCF-AHA), aetiology (HF is the final common pathway of all cardiac diseases), and finally comprehensive management of both acute and chronic HF with evidence-based drug and device therapy.
Exam relevance: HF is one of the most heavily examined topics in HKUMed summative exams — appearing as MCQs (CXR interpretation, drug mechanisms, staging), SAQs (approach to dyspnoea, management algorithms), and minicases/OSCEs (history taking for SOBOE, physical examination findings). Past papers directly test Killip class, CXR signs of pulmonary congestion, NYHA classification, the four pillars of HFrEF therapy, and device indications [3][4][5].
Core Concept 1: What is Heart Failure?
Heart failure is a clinical state in which the heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues despite adequate filling pressure (forward failure/hypoperfusion), and/or can do so only from an elevated filling pressure (backward failure/congestion). [1]
Why Two Parts to the Definition?
The definition captures two distinct haemodynamic problems. Forward failure means cardiac output is inadequate — tissues are under-perfused (shock, oliguria, confusion). Backward failure means blood backs up behind the failing ventricle — causing congestion (pulmonary oedema from left heart, peripheral oedema from right heart). Most patients have predominantly backward failure (congestion), which is why SOBOE is the hallmark symptom. Understanding this duality is critical because management targets differ: congestion → diuretics/vasodilators; low output → inotropes/mechanical support.
- Normal cardiac output ≈ 70 mL/kg/min. For a 70 kg person: CO ≈ 4.9 L/min (~5 L/min). [1]
- The heart's job is to match output to metabolic demand. At rest this is ~5 L/min; during exercise it must increase proportionally.
Left heart backward failure (more common) → Pulmonary congestion Right heart backward failure (more common) → Peripheral congestion Left or right heart forward failure (less common) → Syncope, cardiogenic shock [1]
The mammalian double circulation means the left and right hearts fail in different directions with different clinical consequences:
| Direction | Left Heart | Right Heart |
|---|---|---|
| Backward (congestion) | Blood backs into pulmonary veins → pulmonary oedema → SOB, orthopnoea, PND, pink frothy sputum, basal crepitations | Blood backs into systemic veins → ↑JVP, hepatomegaly, ascites, ankle oedema, pleural effusion |
| Forward (low output) | Reduced systemic perfusion → hypotension, syncope, cardiogenic shock, cold extremities, oliguria, confusion | Reduced pulmonary perfusion → syncope, shock |
Exam Trap
Students often list "ankle oedema" as a sign of left heart failure. Ankle oedema is a sign of right heart failure (or biventricular failure). Pulmonary congestion (crepitations, SOB, orthopnoea) is left heart failure. If the exam gives you bilateral ankle oedema + elevated JVP + hepatomegaly without lung crepitations, think isolated right heart failure (e.g. cor pulmonale, pulmonary hypertension).
Core Concept 2: Why Does HF Cause SOB?
Shortness of breath is a very sensitive symptom indicating interruption of: bringing O₂ into the body, removing CO₂, delivering O₂ to tissues, maintaining bodily pH, or psychological factors. SOB is NOT specific for any individual disease process. [1]
Prior to the optimal point: ↑Venous Return → ↑Stroke Volume/Cardiac Output. After the optimal point: ↑Venous Return → ↓Stroke Volume/Cardiac Output → ↑LVEDV → ↑LVEDP → ↑LA Pressure → ↑Pulmonary Venous Pressure. [1]
Why this matters: The Frank-Starling curve is the single most important physiological concept in HF. A normal heart operates on the ascending limb — more stretch = more output. A failing heart has a flattened curve and is pushed past its optimal point. Any additional preload (e.g. lying flat, fluid overload, high-salt diet) no longer increases output; instead, it increases end-diastolic pressure, which transmits backward to the lungs, causing pulmonary congestion and SOB.
While lying down, loss of gravitational venous blood pooling results in 300-600 mL increase in venous return to the heart, leading to SOB. While sitting up, partial restoration of gravitational venous blood pooling reduces venous return, resolving orthopnoea. [1]
- Orthopnoea: Immediate redistribution of intravascular blood from lower limbs to thorax when supine → overwhelms the failing LV → pulmonary congestion. Relieved within minutes by sitting up.
- PND (Paroxysmal Nocturnal Dyspnoea): Delayed fluid shift from interstitium into circulation over 1-2 hours of lying down → gradual ↑VR → patient wakes gasping. Takes longer to resolve than orthopnoea because the fluid source is interstitial, not intravascular [2].
Normal pulmonary capillary hydrostatic pressure ≈ 7 mmHg. Normal plasma oncotic pressure ≈ 28 mmHg. In left heart failure: ↑LVEDP → hydrostatic pressure rises to ~25-30 mmHg → fluid is forced into the interstitium and alveoli. [1]
This is a direct application of Starling's equation at the pulmonary capillary. Normally, oncotic pressure (28 mmHg) far exceeds hydrostatic pressure (7 mmHg), keeping alveoli dry. When LV failure raises hydrostatic pressure above oncotic pressure, fluid leaks out → interstitial oedema (Kerley B lines on CXR) → alveolar oedema (batwing opacities, pink frothy sputum).
Core Concept 3: Clinical Manifestations of HF
| Symptoms | Signs |
|---|---|
| Dizziness/pre-syncope | Cyanosis |
| Disturbance of consciousness | Hypotension |
| Restlessness | Cold sweat, cold extremities |
| Memory disorder | Oliguria, agitation, confusion |
| Left Heart Failure | Right Heart Failure | |
|---|---|---|
| Symptoms | SOB on exertion, nocturnal cough, pinky foamy sputum, orthopnoea, PND, palpitation | Ankle swelling, abdominal distension, RUQ abdominal pain, anorexia |
| Signs | Tachycardia, lung crepitations, S3 and/or S4, cardiomegaly | Bilateral pitting ankle oedema, hepatomegaly, pleural effusion, elevated JVP, hepatojugular reflux |
High Yield: Predictive Value of HF Symptoms and Signs
No single symptom or sign is both sensitive AND specific for HF. S3 gallop has the highest PPV (61%) but low sensitivity (31%). SOB on exertion is the most sensitive (66%) but least specific (52%). CXR cardiomegaly has moderate sensitivity (62%) and specificity (67%). This is why HF is a CLINICAL diagnosis requiring a combination of features. [1]
| Feature | Sensitivity (%) | Specificity (%) | PPV (%) |
|---|---|---|---|
| SOB on exertion | 66 | 52 | 23 |
| Orthopnoea | 21 | 81 | 2 |
| PND | 33 | 76 | 26 |
| Edema | 23 | 80 | 22 |
| Tachycardia > 100 | 7 | 99 | 6 |
| Basal crackles | 13 | 91 | 27 |
| Ankle edema | 10 | 93 | 3 |
| Gallop (S3) | 31 | 95 | 61 |
| Neck vein distension | 10 | 97 | 2 |
| CXR: cardiomegaly | 62 | 67 | 32 |
Core Concept 4: How to Diagnose HF
HF is a clinical diagnosis. [1]
The lecture references the Framingham Criteria for diagnosing HF. Diagnosis requires 2 major criteria OR 1 major + 2 minor criteria:
| Major Criteria | Minor Criteria |
|---|---|
| PND | Bilateral ankle oedema |
| Neck vein distension | Night cough |
| Rales | Dyspnoea on exertion |
| Cardiomegaly on CXR | Hepatomegaly |
| Acute pulmonary oedema | Pleural effusion |
| S3 gallop | Tachycardia ≥ 120 bpm |
| ↑JVP > 16 cm H₂O | Weight loss ≥ 4.5 kg in 5 days with treatment |
| Hepatojugular reflux |
The Boston Criteria use a scoring system across History, Physical Examination, and CXR criteria. Definite HF: score > 7. Possible HF: 5-7. Unlikely HF: < 5. [1]
Key scoring items from the lecture:
| History | Score | PE | Score | CXR | Score |
|---|---|---|---|---|---|
| Dyspnoea at rest | 4 | Tachycardia 91-110 / > 110 | 1 / 2 | Pulmonary oedema | 4 |
| Orthopnoea | 4 | JVP > 6 cm ± hepatomegaly/oedema | 2 / 3 | Interstitial pulmonary oedema | 3 |
| PND | 3 | Lung crackles basal / > basal | 1 / 2 | Bilateral pleural effusions | 3 |
| Dyspnoea walking level | 2 | Wheezing | 3 | CTR ≥ 0.5 | 3 |
| Dyspnoea climbing | 1 | S3 | 3 | Upper lobe diversion | 2 |
This is extremely high-yield for exams. [1]
| CXR Finding | Left Atrial Pressure |
|---|---|
| Normal | 5-10 mmHg |
| Upper lobe diversion (Cephalization) | 10-15 mmHg |
| Kerley B lines | 15-20 mmHg |
| Pulmonary alveolar oedema (Batwing) | > 25 mmHg |
CXR Findings — Why They Occur
- Upper lobe diversion (cephalization): When hydrostatic pressure exceeds 10 mmHg, fluid leaks into the interstitium and compresses lower lobe vessels (gravity-dependent). Hypoxia also causes vasoconstriction in lower lobe vessels. Blood is redirected to upper lobe vessels, making them appear more prominent than lower lobe vessels (normally lower > upper).
- Kerley B lines (septal lines): Short, white lines perpendicular to the pleural surface at the lung base. They represent thickened interlobular septa due to interstitial oedema. Develop at LA pressure > 15-20 mmHg.
- Batwing/butterfly pattern: Bilateral perihilar alveolar oedema. Occurs when hydrostatic pressure exceeds oncotic pressure (> 25 mmHg), flooding alveoli with fluid.
The lecture includes a slide on JVP assessment. Elevated JVP reflects elevated right atrial pressure, which in the context of HF indicates backward failure of the right heart (or biventricular failure). JVP is measured in cm above the sternal angle with the patient at 45°. Normal is ≤ 3-4 cm above the sternal angle (equivalent to ~8 cm H₂O central venous pressure).
Killip Classification stratifies severity of LV dysfunction and determines clinical status of post-MI patients. [1]
| Class | Description |
|---|---|
| I | No rales, no S3 |
| II | Rales < 50% lung fields or presence of S3 |
| III | Rales > 50% lung fields: pulmonary oedema |
| IV | Cardiogenic shock |
Killip vs NYHA
Killip is specifically for acute post-MI settings. NYHA is for chronic HF functional status. Don't mix them up in exams. If the stem says "post-MI patient," use Killip. If it says "chronic HF patient with exercise limitation," use NYHA.
BNP (Brain Natriuretic Peptide) and NT-proBNP are biomarkers released from cardiomyocytes in response to myocardial wall stress (volume and pressure overload). They have vasodilatory, natriuretic, anti-hypertrophic, anti-fibrotic, and anti-sympathetic effects via NPR-A/cGMP signalling. They are degraded by neprilysin. [1]
Why BNP matters:
- Elevated BNP/NT-proBNP supports a diagnosis of HF, especially when clinical picture is uncertain
- Useful as a rule-out test — a normal BNP makes HF very unlikely (high negative predictive value)
- Should NOT be interpreted in isolation — must be considered alongside all clinical data
Causes for elevated BNP include both cardiac (HF, ACS, valvular disease, AF, myocarditis, LVH) and non-cardiac causes (advancing age, renal failure, anemia, severe pneumonia, pulmonary hypertension, critical illness, sepsis, severe burns). [1]
Exam Trap: Elevated BNP ≠ Heart Failure
Renal failure is the most common non-cardiac cause of elevated BNP/NT-proBNP in clinical practice. Always check the creatinine. Obesity paradoxically LOWERS BNP levels (not on the lecture slide but important clinically — obese patients may have falsely low BNP despite having HF).
Echocardiography is the key investigation for suspected HF. It can identify: pericardial disease (constrictive pericarditis, pericardial effusion), valvular heart diseases (MS/MR, AS/AR), congenital heart diseases (ASD/VSD/PDA), and myocardial disorders (HOCM, HFpEF, HFrEF). [1]
Echocardiography tells you:
- Ejection fraction — distinguishes HFrEF from HFpEF
- Structural cause — valve disease, wall motion abnormalities (ischaemic), hypertrophy, chamber dilatation
- Diastolic function — E/A ratio, tissue Doppler (E/e'), for diagnosing HFpEF
The lecture presents a complete differential framework for SOB on exertion, divided into: Heart Failure, Respiratory Causes, Systemic Causes (anemia, hyperthyroidism, CKD, acidosis, deconditioning), and Psychological Causes. [1]
| Category | Examples | Key Discriminators |
|---|---|---|
| Cardiac | HF (HFrEF, HFpEF), IHD, valvular disease, arrhythmia, pericardial disease | Orthopnoea, PND, S3, elevated JVP, peripheral oedema, cardiomegaly |
| Respiratory | COPD, asthma, ILD, pleural effusion, PE, lung cancer, pneumonia | Wheezing, barrel chest, clubbing (ILD/CA lung), pleuritic pain, cough/sputum |
| Systemic | Anaemia, hyperthyroidism, CKD, metabolic acidosis, deconditioning | Pallor, weight loss, tremor, renal failure, sedentary lifestyle |
| Psychological | Hyperventilation, panic disorder | Perioral/peripheral tingling, no objective desaturation, normal examination |
Differentiating cardiac from respiratory dyspnoea [2]:
| Feature | Cardiac | Respiratory |
|---|---|---|
| PND | Characteristic | Absent |
| Orthopnoea | Characteristic | Possible in COPD (diaphragm splinting) |
| Oedema | Often present | Only if cor pulmonale |
| Associated symptoms | Angina, palpitation | Cough, sputum, wheezing |
| Signs | ↑JVP, S3, basal crepitations, cardiomegaly | Barrel chest, wheezing, hyperinflation |
Core Concept 6: Staging of Heart Failure
NYHA classes define the functional limitation of the patient. [1]
| NYHA Class | Description |
|---|---|
| I | No limitation of physical activity. Ordinary activity does not cause symptoms. |
| II | Slight limitation. Comfortable at rest, but ordinary activity causes symptoms. |
| III | Marked limitation. Comfortable at rest, but less than ordinary activity causes symptoms. |
| IV | Unable to carry on any physical activity without symptoms, or symptoms at rest. |
ACCF/AHA stages capture the progression of HF, including at-risk patients. [1]
| Stage | Description | NYHA Equivalent |
|---|---|---|
| A | At high risk but no structural heart disease or symptoms (e.g. HT, DM, CAD, family history of CMP) | None |
| B | Structural heart disease but no symptoms (e.g. previous MI, LV dysfunction, LVH, asymptomatic valve disease) | I |
| C | Structural heart disease with prior or current symptoms | I-IV |
| D | Refractory HF requiring specialized interventions | IV |
Key Difference: NYHA vs ACCF/AHA
NYHA is bidirectional — a patient can improve from Class III to Class II with treatment. ACCF/AHA stages are unidirectional — once a patient reaches Stage C, they cannot go back to Stage B even if symptoms resolve with treatment. Stage A and B are about prevention; Stage C and D are about treatment. Exams love testing whether a previously symptomatic patient who is now asymptomatic on therapy is Stage C (not Stage B).
Core Concept 7: Causes of Heart Failure
HF is the final common path of ALL cardiac diseases. [1]
| Category | Examples |
|---|---|
| Systemic pressure overload | Hypertension |
| Pulmonary pressure overload | Pulmonary hypertension |
| Myocardial disease | Loss of contractile force (systolic), impaired relaxation (diastolic) |
| Valvular disease | Pressure/volume overload from stenosis/regurgitation |
| Heart rhythm disorders | Bradycardia, tachycardia, loss of AV synchrony, loss of VV synchrony |
| Congenital anomalies | Volume/pressure overload |
| Pericardial disease | Constrictive filling |
This is the most comprehensive list from the lecture and is high-yield. [1]
| Cause | Examples |
|---|---|
| IHD | Stunning, hibernation, microcirculatory disorder |
| Cardiomyopathy | HCM, DCM, RCM, ARVC, non-compaction, Takotsubo, muscular dystrophy, laminopathy |
| Cardiotoxic substances | Alcohol, cocaine, amphetamines, anabolic steroids, heavy metals (Cu, Fe, Pb, Co, Hg), drugs (anthracyclines, immunosuppressants, antidepressants, antiarrhythmics, NSAIDs, anaesthetic agents), radiation |
| Infectious | Myocarditis (viral, bacterial, Rickettsial, Chagas disease) |
| Immune disorder | RA, SLE, polymyositis, mixed connective tissue disease |
| Infiltrative | Sarcoidosis, amyloidosis, haemochromatosis, invasive malignant tumours |
| Metabolic/enzyme | DM, Fabry disease, Pompe disease, Hurler/Hunter syndrome |
| Endocrine | Hyperthyroidism, Cushing disease, phaeochromocytoma, adrenal insufficiency, abnormal GH secretion |
When evaluating a patient with HF, always ask about: established CVD (CAD, PVD, stroke), CV risk factors (HT, smoking, DM, obesity, dyslipidaemia), exposure to cardiotoxic agents (chemotherapy/RT, alcohol, substance abuse), valvular diseases (rheumatic fever, CTD), systemic disorders (thyroid, myopathy, STD, phaeochromocytoma), and family history (CMP, sudden death, myopathy, arrhythmias, premature CVD). [1]
This classification is fundamental and heavily tested. [1]
| HFrEF (≤ 40%) | HFpEF (≥ 50%) | HFmrEF (41-49%) | |
|---|---|---|---|
| Other name | Systolic HF | Diastolic HF | Borderline |
| Age | All ages, typically 50-70 | Frequently elderly | Similar to HFpEF |
| Sex | More often male | Frequently female | — |
| LV size | Usually dilated | Usually normal, often with LVH | — |
| LVH on ECG | Sometimes | Usually | — |
| CXR | Congested with cardiomegaly | Congested with NO cardiomegaly | — |
| Gallop | S3 | S4 | — |
| Key comorbidities | Old MI +++ | HT +++, DM +++, Obesity +++ | — |
| Evidence for treatment | Strong (multiple landmark RCTs) | Limited until recently (SGLTi) | — |
High Yield: S3 vs S4
- S3 = rapid ventricular filling into a dilated, volume-overloaded ventricle → HFrEF
- S4 = atrial contraction against a stiff, non-compliant ventricle → HFpEF (or LVH, HCM)
- S3 has the highest PPV (61%) of any single clinical sign for HF [1]
Basic tests for initial evaluation: Urine (protein, blood, glucose, microscopy), CBC, serum K/Ca/PO₄/Cr/urea/fasting glucose, ECG (LVH, arrhythmia), TSH, CXR, BNP or NT-proBNP. [1]
| Investigation | Why |
|---|---|
| CBC | Anaemia as a precipitant or cause of high-output HF |
| Renal function | CKD as comorbidity; baseline before ACEi/ARB/diuretics |
| Electrolytes | K⁺ monitoring (ACEi/MRA cause hyperkalaemia; diuretics cause hypokalaemia) |
| Fasting glucose | DM is a major RF and comorbidity |
| TSH | Thyroid disease is a reversible cause of HF |
| ECG | LVH, arrhythmia (AF), ischaemia, conduction disease, Q waves (old MI) |
| CXR | Cardiomegaly, pulmonary congestion, pleural effusion |
| BNP/NT-proBNP | Supports diagnosis; high NPV for ruling out HF |
| Echocardiography | Gold standard for assessing EF, structure, valves, diastolic function |
Core Concept 10: Management of Acute Heart Failure
1. Is this acute HF? 2. How severe? 3. Any precipitating cause(s)? 4. Hemodynamic subtype? 5. What are the treatment options? [1]
The lecture references the ESC/ACC mnemonic. Common precipitants include [1]:
- Cardiac: ACS, arrhythmia (especially new AF), valvular emergency, hypertensive crisis
- Systemic: Anaemia, endocrine (thyroid, phaeochromocytoma), adverse drug effects, infection/sepsis, non-compliance with medications or diet (high salt/fluid intake)
- Pulmonary: PE, pneumonia
Warm & Dry | Warm & Wet | Cold & Dry | Cold & Wet [1]
| Adequate Perfusion (Warm) | Inadequate Perfusion (Cold) | |
|---|---|---|
| No Congestion (Dry) | Warm & Dry = Compensated; no acute intervention needed | Cold & Dry = Volume depleted + low output; cautious fluids ± inotropes |
| Congestion (Wet) | Warm & Wet = Most common ADHF presentation; diuretics + vasodilators | Cold & Wet = Worst prognosis; vasodilators + inotropes ± mechanical support |
The lecture's management algorithm for acute HF: [1]
Key medications in acute HF:
| Drug | Mechanism | Purpose |
|---|---|---|
| IV Frusemide | Loop diuretic | ↓Preload by promoting diuresis/natriuresis |
| IV Nitrate (GTN) | Venodilator (low dose) + arteriodilator (high dose) | ↓Preload and ↓afterload |
| Morphine | Venodilation, anxiolysis, ↓respiratory drive | ↓Preload, relieve distress (used cautiously) |
| Dopamine | DA/β₁ agonist (dose-dependent) | Inotrope + renal vasodilation at low dose |
| Dobutamine | β₁ agonist | Inotrope, ↑contractility and CO |
Improve symptoms (congestion and low-output), restore oxygenation, optimize volume status, identify etiology and precipitating factors, optimize chronic oral therapy, minimize side effects, identify candidates for revascularization or device therapy, identify risk of thromboembolism. [1]
At least daily: weight (after voiding in AM), fluid I/O, vital signs, signs (oedema, ascites, rales, hepatomegaly, JVP, hepatojugular reflux), symptoms (orthopnoea, PND, dyspnoea, fatigue), electrolytes (K⁺, Na⁺), renal function (BUN, creatinine). [1]
Core Concept 11: Management of Chronic Heart Failure
Decreased CO → Activation of SNS, RAAS, and vasopressin → ↑HR, ↑contractility, vasoconstriction, ↑circulating volume → Short-term: maintains BP and CO → Long-term: ↑cardiac workload (↑preload and afterload) → Further LV dysfunction → Vicious cycle. [1]
This is the vicious cycle of heart failure. The maladaptive neurohormonal activation that initially compensates for ↓CO eventually causes further harm:
- SNS activation → tachycardia, ↑afterload, myocardial oxygen demand, arrhythmias
- RAAS activation → vasoconstriction, Na⁺/H₂O retention, fibrosis, hypertrophy, ↑aldosterone
- Vasopressin → water retention, hyponatraemia
The natriuretic peptide system (ANP/BNP) is a counter-regulatory mechanism that promotes vasodilation, natriuresis, and inhibits RAAS/SNS. However, it is insufficient to overcome the maladaptive activation.
The paradigm shift in HF therapy: from drugs that simply improve haemodynamics (digoxin, diuretics) to drugs that block neurohormonal maladaptation (ACEi, beta-blockers, MRA, ARNI), which actually reduce mortality. [1]
The lecture presents the evolution and current standard of care. The four pillars that ALL HFrEF patients should receive (unless contraindicated):
| Pillar | Drug Class | Key Evidence | Mortality Benefit |
|---|---|---|---|
| 1. ACE Inhibitor (or ARB if intolerant) | ACEi: Enalapril, Captopril, Ramipril, Trandolapril | SOLVD, SAVE, AIRE, TRACE | RRR 16-27% |
| 2. Beta-Blocker | Carvedilol, Bisoprolol, Metoprolol CR/XL | US Carvedilol, CIBIS-II, MERIT-HF, COPERNICUS | RRR 34-65% |
| 3. MRA | Spironolactone, Eplerenone | RALES, EPHESUS | Significant reduction |
| 4. SGLT2 Inhibitor | Dapagliflozin, Empagliflozin | DAPA-HF, EMPEROR-Reduced | RRR 17% (added to standard therapy) |
ARNI (Sacubitril/Valsartan = Entresto = LCZ696) replaces ACEi as the preferred RAAS blocker based on PARADIGM-HF:
PARADIGM-HF: LCZ696 (Entresto) vs Enalapril in HFrEF (LVEF < 35%). HR 0.80 for CV mortality/HF hospitalization, NNT = 21. Entresto is now recommended in place of ACEi for eligible HFrEF patients. [1]
Detailed Drug Notes
Block conversion of Ang I to Ang II. Recommended for ALL HFrEF patients. Relieve symptoms, improve exercise tolerance, reduce risk of death, decrease disease progression. [1]
| Trial | Drug | N | Criteria | RRR | NNT |
|---|---|---|---|---|---|
| SOLVD | Enalapril | 2569 | LVEF < 35% | 16% | 22 |
| SAVE | Captopril | 2231 | LVEF < 40% | 19% | 24 |
| AIRE | Ramipril | 2006 | Clinical CHF | 27% | 18 |
| TRACE | Trandolapril | 1749 | LVEF < 35% | 22% | 13 |
Block AT1 receptors. Should NOT be considered equivalent or superior to ACEi. Used as ALTERNATIVE when ACEi intolerant (intractable cough or angioedema). [1]
ACEi Cough vs ARB
ACEi inhibits bradykinin breakdown → bradykinin accumulates in lungs → dry cough (up to 20% of patients, more common in Chinese). ARBs don't affect bradykinin metabolism → no cough. However, if patient had angioedema with ACEi, use ARB with caution (small cross-reactivity risk).
Cardioprotective via blockade of excessive SNS stimulation. In the short-term, BB decreases myocardial contractility; increase in EF occurs after 1-3 months of use. START LOW, GO SLOW during initial titration. [1]
| Trial | N | Drug | RR (mortality) |
|---|---|---|---|
| US Carvedilol | 1,094 | Carvedilol | 0.35 |
| CIBIS-II | 2,647 | Bisoprolol | 0.66 |
| MERIT-HF | 3,991 | Metoprolol CR | 0.66 |
| COPERNICUS | 2,289 | Carvedilol | 0.65 |
Exam Trap: Beta-Blockers in Acute HF
Beta-blockers are contraindicated in acutely decompensated HF (they will worsen cardiac output). They should be started only after the patient is euvolaemic and stable. If a patient is already on a beta-blocker and gets admitted with ADHF, you generally continue it (unless in cardiogenic shock) but do NOT uptitrate.
Spironolactone reduces HF-related morbidity and mortality in NYHA III-IV. Side effects: hyperkalaemia and gynaecomastia. Monitor K⁺ and creatinine closely. Eplerenone is a selective MRA with less hormonal side effects, shown to reduce mortality in MI + HF patients. [1]
The combined neprilysin inhibitor (sacubitril) + ARB (valsartan). Sacubitril inhibits neprilysin, the enzyme that degrades natriuretic peptides → ↑BNP/ANP levels → enhanced vasodilation, natriuresis, anti-fibrotic and anti-hypertrophic effects. Combined with ARB to block RAAS.
Cannot give ARNI with ACEi simultaneously (risk of angioedema). Must have a 36-hour washout period when switching from ACEi to ARNI. [1]
DAPA-HF: Dapagliflozin in HFrEF (LVEF < 40%), NYHA II-IV. Reduced composite of worsening HF or CV death. EMPEROR-Reduced: Empagliflozin in HFrEF (EF < 40%). Similar results. [1]
SGLT2 inhibitors also have renal protective effects: DAPA-CKD showed reduced composite renal endpoint in CKD patients regardless of diabetes status. [1]
EMPEROR-Preserved: Empagliflozin in HFpEF (EF > 40%). Reduced composite of CV death or hospitalization for HF — making SGLT2i the FIRST drug class to show benefit in HFpEF. [1]
| Agent | Mechanism | Indication |
|---|---|---|
| Ivabradine | Funny channel (If) blocker → ↓SA node firing (phase 4 depolarization) → ↓HR | NYHA II-IV, LVEF ≤ 35%, sinus rhythm, HR ≥ 70 bpm, intolerant to beta-blockers |
| Vericiguat | Soluble guanylate cyclase stimulator → ↑cGMP → vasodilation | HFrEF with recent hospitalization (VICTORIA study) |
| Hydralazine + Nitrate | Arteriolar vasodilation (hydralazine) + venodilation (nitrate) | Alternative to ACEi/ARB if intolerant; add-on in Black patients |
| Digoxin | ↑Contractility (Na⁺/K⁺ ATPase inhibition), ↓HR in AF | Symptom relief; does NOT reduce mortality |
| Diuretics | ↓Preload, relieve congestion | Symptom relief; ALL patients with fluid overload |
The lecture presents a powerful timeline showing 1-year mortality reduction through successive drug additions:
- Diuretic + Digoxin alone: ~15%
- ACEi (SOLVD 1991): 12.8% → RRR 23%
- Beta-blocker (CIBIS-2 1999): 8.8% → RRR 33%
- ARNI replacing ACEi (PARADIGM-HF 2013): 7.9% → RRR 16%
- SGLTi (DAPA-HF 2019): ~10% → further RRR 17% [1]
Historically limited data and unsatisfactory outcomes. Treatment principles: treat underlying causes (BP control, CAD), treat precipitating factors (AF), relieve symptoms (cautious diuretic use), slow HR to increase diastolic filling time (beta-blocker, verapamil, diltiazem), regress LVH (BP control, ? ACEi/ARB), reduce hospitalization (ARB). Now: SGLT2i (empagliflozin — EMPEROR-Preserved) is the first drug to show benefit. [1]
Non-pharmacological treatments: [1]
| Intervention | Indication |
|---|---|
| Cardiac Resynchronization Therapy (CRT / biventricular pacing) | NYHA III despite optimal medical therapy, sinus rhythm, widened QRS > 120 ms, LVEF < 35%, LVD > 5.5 cm |
| Implantable Cardioverter Defibrillator (ICD) | Secondary prevention of VT/VF; Primary prevention: NYHA II-III, LVEF ≤ 30% (consider 31-35%) |
| CABG | Ischaemic cardiomyopathy with viable myocardium |
| Cardiac Transplantation / LVAD | Refractory heart failure (Stage D) |
ICD Evidence
MADIT-II: Prophylactic ICD in ischaemic LV dysfunction (LVEF ≤ 30%) significantly improved survival compared to conventional therapy. [1]
CRT vs ICD — Don't Confuse Them
CRT is a pacemaker with leads in both ventricles to re-synchronize contraction (for patients with wide QRS/LBBB causing dyssynchronous contraction). ICD detects and terminates lethal arrhythmias (VT/VF) by delivering a shock. Many patients receive a CRT-D (combined device).
The lecture's overall algorithm [1]:
SOBOE → Differential diagnosis (Cardiac / Respiratory / Systemic / Psychological)
→ If cardiac: Heart Failure suspected
→ History + PE + Investigations (ECG, CXR, BNP, Echo)
→ Confirm HF (Framingham/Boston criteria)
→ Stage HF (NYHA + ACCF/AHA)
→ Identify cause(s) of HF
→ Treatment:
→ Drug therapy (Four pillars for HFrEF: ACEi/ARNI + BB + MRA + SGLTi)
→ Device therapy (PPM/CRT, ICD)
→ Surgical therapy (revascularization, valve intervention, LVAD, transplant)Past Paper Themes
2021 MCQ Q82: "Elderly patient with acute SOB. CXR shows bilateral perihilar consolidation, blunting costophrenic angles, cardiomegaly, Kerley B lines, upper lobe venous diversion. Most likely diagnosis?" → Heart failure [3]. This directly tests the CXR-LA pressure correlation table from the lecture.
2022 MCQ Q51: "35-year-old with spondyloarthritis, SOBOE, orthopnoea, early diastolic murmur at left sternal border. Most likely diagnosis?" → Aortic regurgitation [4]. This tests the aetiology of HF — spondyloarthritis is associated with aortitis and AR.
2024 EMQ Q3: "Bilateral fine basal crackles with JVP NOT raised. Most likely diagnosis from a list including cardiomyopathy, COPD, IPF etc." → Idiopathic pulmonary fibrosis (not HF, because JVP is not raised) [5]. This is a key discriminator: bilateral basal crackles with ↑JVP = HF; bilateral basal crackles with normal JVP = ILD/IPF.
2022 SAQ Q2: "45-year-old smoker with progressive exertional dyspnoea and massive right pleural effusion. Name four respiratory symptoms, two systemic symptoms, four physical signs." [6] → Tests the systematic approach to SOB differential.
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MCQ: A 68-year-old man with DM and HT presents with progressive SOBOE, orthopnoea, and bilateral ankle oedema. Echo shows LVEF 30%. CXR shows cardiomegaly and upper lobe diversion. Which NYHA class? Which ACCF/AHA stage? → NYHA III (marked limitation), ACCF/AHA Stage C (structural disease with symptoms).
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SAQ: List the four pillars of guideline-directed medical therapy for HFrEF and name one landmark trial for each. → ACEi/ARNI (PARADIGM-HF), Beta-blocker (CIBIS-II/MERIT-HF), MRA (RALES), SGLTi (DAPA-HF).
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MCQ: CXR shows Kerley B lines. What is the approximate left atrial pressure? → 15-20 mmHg.
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SAQ: Explain the pathophysiology of orthopnoea in left heart failure using the Frank-Starling mechanism. → Supine → loss of gravitational pooling → 300-600 mL ↑venous return → failing LV pushed past optimal point on F-S curve → ↑LVEDP → ↑LA pressure → pulmonary congestion → SOB. Sitting up restores gravitational pooling → ↓VR → relief.
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MCQ: Which physical sign has the highest PPV for HF? → S3 gallop (PPV 61%).
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SAQ: Name five precipitating factors of acute decompensated heart failure. → ACS, arrhythmia (new AF), infection/pneumonia, non-compliance with medication/diet, uncontrolled hypertension, anaemia, thyroid disease, PE, adverse drug effects.
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MCQ: A post-MI patient has rales involving > 50% of lung fields. What Killip class? → Killip III (pulmonary oedema).
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SAQ: What is the mechanism of action of sacubitril/valsartan (Entresto)? Why can it not be given with ACEi? → Sacubitril inhibits neprilysin → prevents degradation of natriuretic peptides (BNP/ANP) → enhanced vasodilation, natriuresis, anti-fibrosis. Valsartan blocks AT1 receptors (RAAS). Cannot combine with ACEi due to risk of life-threatening angioedema from excessive bradykinin accumulation; requires 36-hour washout.
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MCQ: Which class of HF drug was the first to show mortality/hospitalization benefit in HFpEF? → SGLT2 inhibitors (Empagliflozin — EMPEROR-Preserved).
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SAQ: List the indications for CRT in chronic HF. → NYHA III despite optimal medical therapy, sinus rhythm, widened QRS > 120 ms, LVEF < 35%, LV dilatation > 5.5 cm.
High Yield Summary
Heart failure is a clinical syndrome where the heart fails to pump blood at a rate matching metabolic demand, resulting in either forward failure (hypoperfusion/shock) or, more commonly, backward failure (congestion — pulmonary from left heart, peripheral from right heart).
Diagnosis is clinical (Framingham/Boston criteria) supported by CXR (upper lobe diversion at 10-15 mmHg, Kerley B lines at 15-20 mmHg, alveolar oedema at > 25 mmHg), BNP/NT-proBNP (high NPV), and echocardiography (EF, structure, valves).
Staging: NYHA (functional, bidirectional) + ACCF/AHA (structural progression, unidirectional). HFrEF (LVEF ≤ 40%) vs HFpEF (LVEF ≥ 50%) — different demographics, exam findings (S3 vs S4), CXR (cardiomegaly vs no cardiomegaly), and treatment evidence.
Acute HF: Assess haemodynamic profile (Warm/Cold × Wet/Dry). Treat with IV frusemide + IV nitrate ± morphine (if BP stable); inotropes if hypotensive; IABP/ECMO if refractory.
Chronic HFrEF — Four Pillars: ACEi/ARNI + Beta-blocker + MRA + SGLTi. All reduce mortality. ARNI (Entresto) superior to ACEi (PARADIGM-HF). Add ivabradine if HR ≥ 70 in sinus rhythm despite beta-blocker.
HFpEF: Treat underlying cause (BP, CAD, AF). Diuretics for symptoms. SGLT2i is the first class with proven benefit (EMPEROR-Preserved).
Devices: CRT for wide QRS + low EF + NYHA III. ICD for primary prevention (LVEF ≤ 30%). Transplant/LVAD for refractory Stage D.
Active Recall - Shortness of Breath on Exertion: Heart Failure
[1] Lecture slides: GC 084. Shortness of breath on exertion.pdf (all pages) [2] Senior notes: Ryan Ho Cardiology.pdf (p59-60); Ryan Ho Fundamentals.pdf (p204-205, 222-223); Ryan Ho Respiratory.pdf (p19-20); Block A - Shortness of breath on exertion_ heart failure.pdf (p1) [3] Past papers: 2021 Fourth Summative Assessment MCQ.pdf (Q82, p29) [4] Past papers: 2022 Fourth Summative MCQ.pdf (Q51, p20) [5] Past papers: 2024 Fourth Summative MCQ.pdf (Q1-4, p37) [6] Past papers: 2022 Fourth Summative SAQ.pdf (Q2, p3) [7] Lecture slides: CFB (MED05) Cardiovascular (I) Physical Examination (History Taking).pdf (p4) [8] Senior notes: Block A - Cardiology Interactive Tutorial.pdf (p1) [9] Senior notes: Block A – Nephrology Data Interpretation.pdf (p11) [10] Senior notes: Maksim Medicine Notes.pdf (p301)
GC083 Shortness Of Breath In A Construction Site Worker
Acute or subacute dyspnea in a construction worker, typically prompting evaluation for occupational lung diseases such as asbestosis, silicosis, hypersensitivity pneumonitis, or occupational asthma caused by workplace dust and chemical exposures.
GC085 Skin Rash: Doctor I Have A Rash
A skin rash is a visible change in the color, texture, or appearance of the skin—such as redness, bumps, blisters, or scaling—that may indicate underlying dermatologic, infectious, allergic, or systemic disease requiring systematic clinical evaluation.