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MD MEDICINE UNIVERSITY EXAMINATION NOTES

Cardiology - Long & Short Answer Questions

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Q.18 - BLOOD SUPPLY OF HEART, CLASSIFICATION, CLINICAL FEATURES & MANAGEMENT OF MYOCARDIAL INFARCTION (20 Marks)

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PART A: BLOOD SUPPLY OF THE HEART

Coronary Arteries

AORTA (Sinus of Valsalva)
        |
   _____|_____
  |           |
LEFT           RIGHT
CORONARY       CORONARY
ARTERY (LCA)   ARTERY (RCA)
  |
  |___________________________
  |                           |
Left Anterior                Left Circumflex
Descending (LAD)             Artery (LCx)
  |                           |
  |- Ant. IVS                 |- Lateral wall
  |- Ant. LV wall             |- Posterior wall
  |- Apex                     |- SA node (40%)
  |- Bundle of His
  |- AV node (60%)
  
RIGHT CORONARY ARTERY (RCA)
  |
  |___________________________
  |              |            |
Posterior        SA node    AV node
Descending (PDA) (60%)     (80-90%)
(dominant in 85%)

Territories of Supply

Coronary Dominance

• Right dominant (85%): RCA gives PDA
• Left dominant (8%): LCx gives PDA
• Co-dominant (7%): Both supply

Venous Drainage

• Coronary sinus → Right atrium (major, 75%)
• Thebesian veins → directly into cardiac chambers
• Anterior cardiac veins → directly into RA

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PART B: MYOCARDIAL INFARCTION (MI)

Definition

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CLASSIFICATION OF MI

Type 1 - Spontaneous MI

Type 2 - Demand-Supply Mismatch

Type 3 - MI causing Sudden Death

Type 4a - PCI-related MI

Type 4b - Stent thrombosis

Type 5 - CABG-related MI

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By ECG Pattern

MI
|
|_________________________
|                         |
STEMI                     NSTEMI/UA
(ST Elevation MI)         (Non-ST Elevation)
|                         |
Full thickness            Subendocardial
(Transmural)              infarct
|
Pathological Q waves
develop (>40ms, >25% R)

By Territory (STEMI)

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PATHOPHYSIOLOGY FLOWCHART

Atherosclerotic Plaque (Lipid core + Fibrous cap)
              |
         Plaque Rupture / Erosion
              |
    Platelet adhesion & aggregation
              |
    Thrombus Formation (Total/Partial)
              |
    Coronary Occlusion / Critical Stenosis
              |
    Myocardial Ischemia (within 20 sec)
              |
    ATP depletion → Na-K pump fails → Cell swelling
              |
    20-40 min: Reversible injury (angina)
              |
    >40-60 min: IRREVERSIBLE NECROSIS
              |
    Coagulation necrosis (histologic at 6h)
              |
    Neutrophil infiltration (24-72h)
              |
    Macrophage phagocytosis (Days 3-10)
              |
    Granulation tissue (1-2 weeks)
              |
    Scar formation (4-6 weeks)

Wavefront of Necrosis: Subendocardium → Epicardium (inside-out)

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CLINICAL FEATURES

Symptoms

1. Chest pain - Severe, crushing, retrosternal, radiates to left arm/jaw/back; >30 min; not relieved by nitrates
2. Associated: Profuse sweating (diaphoresis), nausea/vomiting, breathlessness
3. Autonomic: Palpitations, syncope
4. Atypical presentations: Epigastric pain, jaw pain alone (especially elderly, diabetics)
5. Silent MI: 20-30% cases (diabetics, elderly women)

Signs

• Tachycardia (or bradycardia in inferior MI)
• Hypotension (cardiogenic shock in severe cases)
• S4 gallop (reduced compliance)
• S3 gallop (if LV failure)
• Pericardial friction rub (day 2-3 in transmural MI)
• Soft S1
• Basal crepitations (if pulmonary oedema)
• Cold clammy skin

ECG Evolution in STEMI

Minutes:   Tall peaked T waves (hyperacute T)
           |
Hours:     ST elevation (convex upward), reciprocal ST depression
           |
12-24h:   Q wave formation, T-wave inversion begins
           |
Days:     Q wave deepens, ST returns to baseline, T-wave inverted
           |
Weeks:    T-wave normalises, Q wave persists (permanent scar marker)

Biomarkers

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KILLIP CLASSIFICATION (Severity of LV Failure in MI)

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COMPLICATIONS OF MI

MI COMPLICATIONS
     |
     |_____________________________________________
     |              |              |              |
  ELECTRICAL    MECHANICAL     EMBOLIC       INFLAMMATORY
     |              |              |              |
  VF (48h)     Rupture:       Mural        Pericarditis
  VT           - Free wall     thrombus     (2-3d)
  AF           - IVS           → Stroke     Dressler's
  AV blocks    - Papillary     → PE         syndrome
  (inf. MI)      muscle                     (2-10 wks)
               LV aneurysm
               Cardiogenic
               shock

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MANAGEMENT OF MI

STEMI Management Flowchart

Suspected STEMI
      |
   12-lead ECG within 10 min
      |
   ________________________
   |                      |
< 12 hrs onset          > 12 hrs / late
      |                      |
Primary PCI available?     Medical Rx only
      |                      (unless ongoing ischaemia)
  ____|____
  |       |
YES       NO
(<120min)  (>120min
   |        door-to-balloon)
Primary      |
PCI          Thrombolysis
   |         (Alteplase/Streptokinase)
   |               |
   |         TIMI flow 2-3?
   |               |
   |          _____|_____
   |          |         |
   |        YES (rescue  NO (failed thrombolysis)
   |          PCI)       → Emergency PCI
   |
   ANTIPLATELET: Aspirin 300mg + Ticagrelor/Clopidogrel
   ANTICOAGULANT: UFH/LMWH/Fondaparinux
   STATIN: High intensity (Rosuvastatin/Atorvastatin)
   BETA-BLOCKER: (if no contraindication)
   ACE INHIBITOR: (start within 24h)
   NITRATES: IV GTN (for pain, not as routine)
   OXYGEN: Only if SpO2 <94%
   MORPHINE: 4-8mg IV (for pain; caution with ticagrelor)

NSTEMI/UA Management (GRACE Score guided)

All patients:
   Aspirin + P2Y12 inhibitor (Ticagrelor preferred)
   Anticoagulation: Fondaparinux (preferred) / LMWH / UFH
   Beta-blocker + Statin + ACE inhibitor

GRACE Score > 140 (High risk): Early invasive strategy (<24h)
GRACE Score 109-140 (Intermediate): Invasive strategy (<72h)
GRACE Score < 109 (Low risk): Conservative strategy

Long-Term Secondary Prevention (ABCDE)

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Q.20 - HOCM: PATHOPHYSIOLOGY, CLINICAL FEATURES, MANAGEMENT + CLASSIFICATION OF CARDIOMYOPATHIES (20 Marks)

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CLASSIFICATION OF CARDIOMYOPATHIES

WHO/ESC Classification

CARDIOMYOPATHIES
         |
    _____|_________________________________________
    |           |           |           |         |
DILATED    HYPERTROPHIC  RESTRICTIVE  ARRHYTHMO- UNCLASSIFIED
(DCM)      (HCM/HOCM)    (RCM)       GENIC RV   (Non-
    |           |           |       Cardiomyo-   compaction,
Systolic    Diastolic   Both         pathy       Stress/
dysfunc.    dysfunc.    walls       (ARVC/D)     Takotsubo)

Key Differences

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HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM)

Definition

Genetics

• Autosomal dominant, incomplete penetrance
• Most common: Beta-myosin heavy chain gene (MYH7, Chr 14) - 35-40%
• Cardiac myosin binding protein C (MYBPC3) - 20-30%
• Others: Troponin T (TNNT2), Troponin I (TNNI3), alpha-tropomyosin

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PATHOPHYSIOLOGY

GENETIC MUTATION (Sarcomere protein genes)
              |
         Abnormal sarcomere function
              |
    Compensatory myocyte hypertrophy
              |
    ASYMMETRIC SEPTAL HYPERTROPHY (IVS > 15mm)
              |
    __________|___________
    |                    |
LVOT OBSTRUCTION    DIASTOLIC DYSFUNCTION
    |                    |
Basal IVS bulges    Impaired relaxation
into LVOT           + Reduced compliance
    |                    |
Venturi effect      ↑ LVEDP
    |                    |
Anterior motion of  Pulmonary hypertension
Mitral valve (SAM)  |
    |               Breathlessness
Worsening LVOT
obstruction
    |
Pressure gradient
(resting or provokable
>30 mmHg)
    |
↓ Stroke Volume
↓ Cardiac Output
    |
Syncope / Presyncope
    |
Myocardial ischemia
(supply-demand mismatch
+ small vessel disease)
    |
Arrhythmias (AF, VT)
    |
Sudden Cardiac Death

SAM (Systolic Anterior Motion) Mechanism

• During systole, elongated anterior mitral leaflet is dragged into LVOT by Venturi forces
• This worsens LVOT obstruction
• Also causes MITRAL REGURGITATION (posterior jet, systolic murmur)

Factors Affecting LVOT Gradient

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CLINICAL FEATURES

Symptoms (Triad: DOE, Angina, Syncope)

1. Dyspnoea on exertion (most common) - due to diastolic dysfunction + LVOT obstruction
2. Angina - small vessel disease + increased demand
3. Syncope/Pre-syncope - LVOT obstruction, arrhythmias (often exertional)
4. Palpitations - AF, NSVT, VT
5. Sudden cardiac death (most dramatic; often first presentation in young athletes!)

Signs

1. Pulse: Bifid (bisferiens) pulse - double peak in carotid (spike + dome)
2. Apex beat: Double impulse (atrial kick + ventricular impulse)
3. Murmur:
   • Ejection systolic murmur at LLSE (LVOT obstruction)
   • Increases with Valsalva, standing
   • Decreases with squatting, handgrip
   • Separate pansystolic murmur (MR - at apex)
4. S4 gallop (atrial contraction into non-compliant LV)
5. No ejection click (differentiates from AS)
6. JVP: Prominent 'a' wave

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INVESTIGATIONS

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MANAGEMENT

Treatment Algorithm

HOCM - All patients
        |
   General Measures:
   - Avoid dehydration, alcohol, Valsalva
   - Avoid competitive sports
   - Genetic counselling + family screening
   - Avoid vasodilators, nitrates, digoxin, diuretics (cautious)
        |
   Symptomatic?
        |
    ____|____
    |       |
   YES      NO (Asymptomatic)
    |       |
    |    Annual follow-up, no specific Rx
    |
LVOT gradient >30 mmHg?
    |
  YES
    |
FIRST LINE: BETA-BLOCKERS
(Metoprolol/Propranolol - ↓HR, ↓contractility, ↑diastole)
OR
NON-DIHYDROPYRIDINE CCB: Verapamil/Diltiazem
(If beta-blockers not tolerated)
    |
Refractory / Severe obstruction (gradient >50 mmHg)?
    |
  YES
    |
Disopyramide (Class IA antiarrhythmic)
+ Beta-blocker combination
    |
Still refractory?
    |
SEPTAL REDUCTION THERAPY
    |
    |_________________________
    |                         |
Surgical Septal Myectomy    Alcohol Septal Ablation
(Morrow procedure)          (ASA - catheter based)
GOLD STANDARD               Suitable for older patients
Low mortality (<1%)         or poor surgical candidates
    |
Cardiac Transplantation (end-stage)

SCD Prevention

ICD IMPLANTATION - Indicated if:
- Prior cardiac arrest / VF
- Spontaneous sustained VT
- Family history of SCD (first-degree relative)
- Unexplained syncope (not vasovagal)
- Massive hypertrophy (max wall thickness ≥30 mm)
- NSVT on Holter
- Abnormal BP response to exercise
- LGE on CMR >15% of LV mass
(Use HCM Risk-SCD Calculator for 5-year risk; ICD if >6%)

Management of Specific Complications

• AF: Rate control (beta-blocker/verapamil) + anticoagulation (OAC) - Cardioversion if haemodynamically unstable
• Heart Failure: Transplantation if end-stage
• Infective endocarditis: Prophylaxis for high-risk dental procedures

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Q.21 - COMPLICATIONS OF INFECTIVE ENDOCARDITIS (Short/Medium Answer)

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COMPLICATIONS OF INFECTIVE ENDOCARDITIS

Overview

MECHANISMS OF COMPLICATIONS
           |
     ______|_______________________________________________
     |            |                  |                   |
BACTERAEMIA  EMBOLIZATION    IMMUNE COMPLEX        CARDIAC
(Sepsis)     (Vegetation      DEPOSITION           DESTRUCTION
     |        fragments)           |                   |
Septic        |            Glomerulonephritis     Valve destruction
metastases    |            Vasculitis             → Regurgitation
Psoas         |            Arthritis             AV conduction block
abscess       |            Splenomegaly          Myocarditis
              |                                   Myocardial abscess
    __________|_____________
    |          |     |     |
  Brain    Lungs  Kidney  Spleen  Skin  Retina

Cardiac Complications

1. Valvular destruction - acute severe regurgitation (AR, MR) → sudden heart failure
2. Perivalvular/Ring abscess - especially aortic root; PR prolongation on ECG
3. Myocarditis/Pericarditis - extension of infection
4. Intracardiac fistula - severe hemodynamic compromise
5. Conduction abnormalities - new AV block in aortic IE = abscess formation (surgical urgency!)
6. Papillary muscle dysfunction - MR

Embolic Complications

Peripheral Signs (Immune-mediated + Embolic)

1. Osler's nodes - painful, tender nodules on finger/toe pulps (immune complex)
2. Janeway lesions - painless, erythematous/hemorrhagic spots on palms/soles (embolic microabscesses)
3. Roth spots - oval retinal hemorrhages with pale center (fundoscopy)
4. Splinter hemorrhages - subungual hemorrhages (linear, dark)
5. Clubbing (chronic IE)
6. Petechiae - conjunctiva, skin, mucous membranes

Renal Complications

1. Immune complex glomerulonephritis - haematuria, proteinuria, AKI
2. Embolic infarcts - loin pain, haematuria
3. Drug nephrotoxicity (aminoglycosides)
4. Interstitial nephritis (beta-lactams)

Neurological Complications

1. Embolic stroke (most common CNS complication, 15-20%)
2. Intracranial mycotic aneurysm - risk of SAH
3. Brain abscess
4. Meningitis (aseptic or bacterial)
5. Toxic encephalopathy
6. Seizures

Musculoskeletal

1. Septic arthritis
2. Osteomyelitis
3. Psoas/epidural abscess (vertebral disc infection - Staphylococcus)
4. Back pain (vertebral osteomyelitis - commonest musculoskeletal complication)

Indications for Emergency Surgery in IE

• Acute severe valvular regurgitation causing heart failure (most common)
• Uncontrolled infection (perivalvular abscess, fistula, progressive destruction)
• Large vegetation (>10 mm) with high embolic risk
• Fungal endocarditis (rarely cured medically)
• Prosthetic valve endocarditis with dehiscence
• New AV block suggesting aortic root abscess

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Q.22 - CONDUCTION SYSTEM OF HEART + TACHYARRHYTHMIAS + BROAD COMPLEX TACHYCARDIA (20 Marks)

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PART A: CONDUCTION SYSTEM OF THE HEART

Components and Anatomy

CONDUCTION SYSTEM
         |
    SA NODE
    (Sinus Node - Keith & Flack)
    - Location: Junction of SVC and RA (Crista terminalis)
    - Blood supply: SA nodal artery (RCA 60%, LCx 40%)
    - Automaticity: 60-100 bpm (dominant pacemaker)
    - Action potential: Slow response (ICa-L, If)
         |
    INTERNODAL TRACTS
    (Bachmann's bundle to LA; internodal pathways to AV node)
         |
    AV NODE
    (Atrioventricular Node - Aschoff-Tawara node)
    - Location: Triangle of Koch (tendon of Todaro + TV septal
      leaflet + coronary sinus ostium)
    - Blood supply: AV nodal artery (RCA 80-90%, LCx 10-20%)
    - Automaticity: 40-60 bpm (secondary pacemaker)
    - KEY FUNCTION: Delay conduction (PR interval 0.12-0.20s)
      Allows atrial contraction before ventricular
         |
    BUNDLE OF HIS
    - Only normal AV conduction pathway
    - Blood supply: LAD + AV nodal artery (double supply)
         |
         |_________________
         |                |
    LEFT BUNDLE         RIGHT BUNDLE
    BRANCH (LBB)        BRANCH (RBB)
         |
    _____|_____
    |         |
  LAF        LPF
(Left      (Left
Anterior   Posterior
Fascicle)  Fascicle)
         |
    PURKINJE FIBERS
    - Automaticity: 20-40 bpm (tertiary pacemaker)
    - Rapid conduction throughout ventricles
    - Endocardium → Epicardium conduction
         |
    VENTRICULAR MUSCLE DEPOLARIZATION
    (QRS: 0.06-0.10s)

Key ECG Intervals

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PART B: TACHYARRHYTHMIAS

Classification Flowchart

TACHYARRHYTHMIAS (HR > 100 bpm)
          |
     _____|______________
     |                  |
NARROW QRS           BROAD QRS
(<120 ms)            (>120 ms)
     |                  |
     |         (See Broad Complex section)
     |
  Origin = SUPRAVENTRICULAR (SVT)
     |
     |___________________________________
     |               |                 |
  SINUS         ATRIAL          JUNCTIONAL
  TACHYCARDIA      |                 |
  (P wave same  ____|____        AVNRT (most
  morphology)   |       |        common SVT)
               AF       AT       AVRT (WPW)
                     Flutter    Junctional
                                tachycardia

Common SVTs

1. Sinus Tachycardia

• Normal P waves, PR normal, gradual onset
• Causes: Pain, fever, anaemia, hyperthyroidism, PE, sepsis, anxiety
• Treatment: Treat underlying cause

2. Atrial Fibrillation (AF)

• Irregularly irregular rhythm
• No identifiable P waves, fibrillatory baseline
• Ventricular rate variable (100-180 bpm if uncontrolled)
• Classification: Paroxysmal (<7d), Persistent (>7d), Long-persistent (>1 yr), Permanent
• Management:
  • Rate control: Beta-blocker / Digoxin / Non-DHP CCB
  • Rhythm control: DC cardioversion / Amiodarone / Flecainide
  • Anticoagulation: CHA₂DS₂-VASc ≥2 (M) / ≥3 (F) → OAC (DOAC preferred)

3. Atrial Flutter

• Regular atrial rate ~300 bpm, with 2:1 block → ventricular rate 150 bpm
• Sawtooth flutter waves (best seen II, III, aVF)
• Management: Rate control; DC cardioversion; catheter ablation (RA isthmus - highly effective)

4. AVNRT (AV Nodal Reentrant Tachycardia)

• Most common SVT (60%)
• Re-entry within AV node (slow + fast pathways)
• P waves buried in or just after QRS (RP < 70 ms)
• Management: Valsalva → Adenosine (6-12 mg IV bolus) → Beta-blocker/CCB → RF ablation

5. AVRT (AV Reentrant Tachycardia) / WPW

• Accessory pathway (Bundle of Kent)
• Pre-excitation: Short PR + Delta wave + wide QRS (WPW)
• Orthodromic AVRT: Narrow QRS (most common in WPW)
• Antidromic AVRT: Wide QRS
• DANGER: AF + WPW → very rapid ventricular rate → VF!
• Management: Adenosine (for orthodromic), RF ablation (definitive); AVOID Digoxin/Verapamil in WPW + AF

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PART C: BROAD COMPLEX TACHYCARDIA (BCT)

Definition

Differential Diagnosis

BROAD COMPLEX TACHYCARDIA
           |
    _______|_________________________
    |               |               |
VENTRICULAR     SVT WITH        SVT WITH
TACHYCARDIA     ABERRANCY      PRE-EXCITATION
(VT - 80%)      (BBB)          (Antidromic AVRT/
    |            (15-20%)       AF in WPW - 5%)
Most dangerous

Distinguishing VT from SVT with Aberrancy

Brugada Criteria (Step-by-Step Algorithm)

Step 1: No RS complex in any V lead?
         → YES = VT
         → NO ↓
Step 2: RS interval > 100ms in any V lead?
         → YES = VT
         → NO ↓
Step 3: AV Dissociation?
         → YES = VT
         → NO ↓
Step 4: LBBB criteria in V1-V2 + RBBB criteria in V6
         (morphology criteria)?
         → YES = VT
         → NO = SVT with aberrancy

Classic ECG Features Favouring VT

Ventricular Tachycardia (VT) Classification

VT
|
|_________________________
|                         |
Non-sustained             Sustained
(< 30 sec, spontaneous)   (>30 sec or
                          haemodynamically
                          unstable)
                               |
                    ___________|___________
                    |                     |
              MONOMORPHIC              POLYMORPHIC
              (one QRS morphology)         |
                    |                 Torsades de Pointes
              Usually structural          (TdP - prolonged QT)
              heart disease (IHD)         |
                                     Helical QRS twisting
                                     around isoelectric line

Management of BCT

BROAD COMPLEX TACHYCARDIA
          |
   Is Patient Haemodynamically Stable?
          |
     _____|_____
     |         |
    NO        YES
     |         |
Immediate     Is it VT or SVT?
Synchronised       |
DC Cardioversion  If uncertain: Treat as VT
(200J biphasic)        |
                   VT Confirmed
                       |
     IV Amiodarone 300mg over 20-60 min
     (then 900mg over 24h)
                       |
               If No Response
                       |
          Synchronised DC Cardioversion
                       |
          If LQTS / Torsades de Pointes:
          - STOP offending drug
          - IV Magnesium sulphate 2g over 10 min
          - Isoprenaline / Pacing (increase HR)
          - Avoid amiodarone (prolongs QT further)

Long-Term VT Management

• ICD (Implantable Cardioverter-Defibrillator): Gold standard for sustained VT/SCD survivors
• Catheter ablation: For recurrent monomorphic VT (especially idiopathic RVOT-VT or post-MI scar)
• Amiodarone: If ICD not available or as adjunct
• Treat underlying cause (revascularisation, HF optimisation)

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Q.23 - DIGOXIN (6 Marks - Short Answer)

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DIGOXIN

Source

Mechanism of Action

DIGOXIN MECHANISM
        |
        |_____________________
        |                    |
POSITIVE INOTROPIC      NEGATIVE CHRONOTROPIC
EFFECT                  & DROMOTROPIC
        |                    |
Inhibits Na-K ATPase    Vagomimetic effect
pump on myocytes        (↑ vagal tone)
        |                    |
↑ Intracellular Na+    ↓ SA node automaticity
        |                    |
Na-Ca exchanger        ↓ AV node conduction
(reverse)
        |
↑ Intracellular Ca²+
        |
↑ Actin-myosin
cross-bridge formation
        |
↑ Contractility

Pharmacokinetics

• Oral bioavailability: 70-80%
• Protein binding: 25%
• Volume of distribution: Large (7 L/kg) - distributed to heart, skeletal muscle
• Elimination: Renal (unchanged) - 60-80%
• Half-life: 36-48 hours (prolonged in renal failure)
• Therapeutic window: 0.5-2.0 ng/mL (very narrow)

Indications

1. Atrial Fibrillation - ventricular rate control (NOT rhythm control)
2. Heart Failure with reduced EF (HFrEF) - especially with AF; improves symptoms, reduces hospitalisations; does NOT reduce mortality
3. Atrial flutter (less preferred)

Drug Interactions (Important)

Digoxin Toxicity

Predisposing Factors

• Renal failure (reduced excretion)
• Hypokalaemia, hypomagnesaemia, hypercalcaemia
• Hypothyroidism
• Old age

Features of Toxicity

1. GI: Nausea, vomiting, anorexia, abdominal pain (earliest)
2. CNS: Visual disturbances (yellow-green halos - xanthopsia), confusion, fatigue
3. Cardiac: Almost any arrhythmia -
   • Most classic: PAT (Paroxysmal Atrial Tachycardia) with AV block
   • Bidirectional VT (pathognomonic)
   • AF → regularisation (complete AV block + junctional rhythm)
   • Bradyarrhythmias, heart block

Management of Toxicity

1. Stop digoxin immediately
2. Correct electrolytes (especially K+ and Mg²+)
3. Monitor ECG continuously
4. For life-threatening arrhythmias: Digoxin-specific antibody fragments (Digibind/DigiFab) - definitive treatment
5. Temporary pacing if severe bradycardia
6. Lignocaine/phenytoin for VT (avoid quinidine, amiodarone initially)

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Q.24 - MASKED HYPERTENSION (6 Marks - Short Answer)

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MASKED HYPERTENSION

Definition

Prevalence

• Estimated 10-30% of general population with normal clinic BP
• Higher in: Men, smokers, diabetics, chronic kidney disease, high alcohol intake

Diagnosis

CLINIC BP
    |
Normal (<140/90)
    |
Risk factors or end organ damage present?
    |
   YES
    |
AMBULATORY BLOOD PRESSURE MONITORING (ABPM)
- Daytime mean >135/85 mmHg = Masked Hypertension
OR
HOME BLOOD PRESSURE MONITORING (HBPM)
- Mean >135/85 mmHg = Masked Hypertension
    |
Confirm with repeat ABPM

Types of Masked Hypertension

Significance / Why It Matters

• Cardiovascular risk equivalent to sustained hypertension
• 2x increased risk of cardiovascular events compared to normotensives
• Associated with left ventricular hypertrophy, carotid IMT thickening
• Often missed because clinic measurement appears normal!
• Risk of end-organ damage (CKD, stroke, MI, retinopathy) similar to sustained HTN

Conditions Associated with Masked Hypertension

1. Diabetes mellitus
2. Chronic kidney disease
3. Obesity
4. Obstructive sleep apnoea
5. High physical activity jobs (sustained adrenergic activation)
6. Excessive alcohol/caffeine/smoking
7. Anxiety disorders

Management

1. Lifestyle modifications (same as for hypertension):
   • Salt restriction (<5g/day)
   • DASH diet
   • Weight loss
   • Exercise (aerobic 150 min/week)
   • Alcohol restriction
   • Smoking cessation
2. Antihypertensive therapy if ABPM confirms persistent elevation:
   • Prefer long-acting agents (24-hour coverage)
   • ACE inhibitors/ARBs (especially if diabetes or CKD)
   • CCBs (for morning surge)
   • Consider agents with once-daily dosing and sustained efficacy
3. Monitoring: Regular HBPM or ABPM every 6-12 months

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Q.25 - MECHANISM OF HYPERTENSION & MANAGEMENT (20 Marks)

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MECHANISM OF HYPERTENSION

Definition

Classification

Primary (Essential) Hypertension - 90-95%

Multifactorial Pathogenesis

MECHANISMS OF ESSENTIAL HYPERTENSION
                |
    ____________|_________________________________
    |           |           |          |         |
RENIN-     SYMPATHETIC   VASCULAR   GENETIC   SODIUM
ANGIOTENSIN  NERVOUS     STRUCTURAL  FACTORS  RETENTION
ALDOSTERONE  SYSTEM      CHANGES
SYSTEM       ACTIVATION      |
    |            |       Arteriolar
    |            |       remodelling
  Ang II      Norepi   (↑ wall:lumen)
    |            |           |
  ↑ SVR      ↑ CO +        ↑ TPR
    |         ↑ TPR
  Aldosterone
    |
  Salt + Water
  Retention
    |
  ↑ Blood Volume
    |
  ↑ CO
    |
  ↑ BP

1. RAAS Pathway (Most Important)

Angiotensinogen (liver)
        |
     RENIN (kidney juxtaglomerular cells)
     [Released by: ↓BP, ↓Na, sympathetic activation]
        |
  Angiotensin I
        |
     ACE (Lung, endothelium)
        |
  ANGIOTENSIN II
     |______________|______________
     |              |             |
  AT1 receptor   Adrenal       CNS
  (Vascular SM)   cortex        |
     |              |        ↑ Sympathetic
  Vasoconstriction  Aldosterone  ↑ ADH
  ↑ TPR             |            |
                 Na+ retention  ↑ Thirst
                 K+ excretion   ↑ Blood Volume
                 ↑ Blood vol

2. Sympathetic Nervous System

SNS Activation (stress, pain, obesity, OSA, renal ischaemia)
        |
Increased Noradrenaline
        |
   _____|______________
   |          |       |
Alpha-1       Beta-1   Beta-1
(Vessels)     (Heart)  (Kidney JGA)
   |          |            |
Vasoconstriction ↑HR + ↑CO  ↑ Renin release
↑ TPR                        ↑ Ang II

3. Renal Mechanisms

Pressure-Natriuresis Curve Reset (Guyton's Theory)
        |
Higher BP needed to excrete same sodium load
        |
Due to: Renal microvascular disease, reduced nephron number
        |
Na+ and water retention → ↑ Blood volume → ↑ CO → ↑ BP

4. Endothelial Dysfunction

NORMAL: Nitric Oxide (NO) → vasodilation
        Prostacyclin (PGI2) → vasodilation

HYPERTENSION:
↓ NO bioavailability (oxidative stress destroys NO)
↑ Endothelin-1 (potent vasoconstrictor)
↑ Angiotensin II (further impairs endothelium)
    → ↑ TPR → ↑ BP

5. Other Mechanisms

• Insulin resistance/Hyperinsulinaemia: Activates SNS, promotes Na retention
• Inflammation: CRP, IL-6, TNF-alpha promote endothelial dysfunction
• Vascular stiffness: ↑ Pulse wave velocity → isolated systolic HTN (elderly)
• Genetic factors: Polymorphisms in AGT, ACE, ADD1 genes

Secondary Hypertension - 5-10%

---

MANAGEMENT OF HYPERTENSION

General Treatment Goals

• Target BP: <140/90 mmHg (general), <130/80 mmHg (high risk: diabetes, CKD, CVD)
• Elderly >80 years: <150/90 mmHg

Step 1: Lifestyle Modifications (ALL patients)

LIFESTYLE CHANGES (Reduce SBP by...)
        |
  ______|_________________________________________
  |         |          |          |          |
  Salt      Weight     Exercise   Alcohol    Smoking
 restriction loss      DASH diet  reduction  cessation
(<5g/d)     ↓10kg      150 min   <2 units   
  ↓5mmHg    ↓5-10mmHg  aerobic/wk  /day
                        ↓7mmHg    ↓3mmHg

Pharmacological Management Flowchart

Newly Diagnosed Hypertension
          |
  Not Black + not CKD + Not DM    Black/Afro-Caribbean
          |                                |
  ACEi or ARB                          CCB or Thiazide
  (If <55y / DM / CKD)                 (not RAA system)
          |
  CCB (if >55y or Black)
          |
STEP 2 (BP not at target):
  ACEi/ARB + CCB
          |
STEP 3:
  ACEi/ARB + CCB + Thiazide-like diuretic
  (Indapamide / Chlorthalidone preferred over HCTZ)
          |
STEP 4 (Resistant HTN - BP uncontrolled on 3 drugs):
  Add 4th agent:
  - K+ >4.5: Alpha-blocker (Doxazosin) or Beta-blocker
  - K+ ≤4.5: Low-dose Spironolactone (25-50mg) - MOST EFFECTIVE
          |
  Seek specialist advice / Investigate for secondary cause

Drug Classes: Mechanism & Key Points

Hypertensive Emergency vs. Urgency

HYPERTENSIVE CRISIS (BP >180/120)
          |
     _____|_______
     |           |
EMERGENCY      URGENCY
(Acute target  (No target
organ damage)  organ damage)
     |               |
Organ damage:    Lower BP slowly
- Hypertensive   over 24-48h
  encephalopathy  oral drugs
- LVF/APO
- ACS
- Aortic dissection
- Eclampsia
- NAHI
     |
ICU admission
IV drugs:
- Labetalol IV
- Nicardipine IV
- Sodium nitroprusside
  (Caution: cyanide toxicity)
- Hydralazine (pregnancy/eclampsia)
- Aortic dissection: ↓ SBP to <120
  in 20 min: Labetalol + Morphine
     |
Reduce MAP by max 25% in first hour
Then gradually to 160/100 over 2-6h

Special Situations

---

QUICK REFERENCE SUMMARY TABLE

---

Sources: Braunwald's Heart Disease (9780323722193); Goldman-Cecil Medicine (9780323930345); Guyton & Hall Medical Physiology (9780443111013); Textbook of Family Medicine (9780323239905); Robbins Basic Pathology (9780323790185)

---

MD MEDICINE UNIVERSITY EXAMINATION NOTES

Cardiology - Questions 26, 27 & Drug Short Answers

---

Q.26 - ETIOPATHOGENESIS, CLASSIFICATION, CLINICAL PRESENTATION, DIAGNOSIS & TREATMENT OF CONGESTIVE HEART FAILURE (20 Marks)

---

DEFINITION

---

ETIOLOGY / CAUSES

Primary Cardiac Causes

ETIOLOGY OF CHF
         |
    _____|___________________________________________
    |           |          |           |           |
ISCHEMIC    HYPERTENSIVE  VALVULAR  MYOCARDIAL  ARRHYTHMIC
    |           |             |           |           |
Coronary    Systemic/     Mitral/     Cardiomyo-  AF with RVR
Artery      Pulmonary     Aortic      pathies:    VT/VF
Disease     HTN           Stenosis/   - DCM       Persistent
(Most       (Increased    Regurgit.   - HCM       tachycardia
common      afterload)               - RCM
cause)                               - ARVC

Common Causes by Category

Precipitating Factors (Cause Decompensation)

PRECIPITANTS OF ACUTE DECOMPENSATION
  (Remember: FAILURE mnemonic)
F - Forgot medications (non-compliance - #1)
A - Arrhythmia (especially AF with rapid rate)
I - Infection (pneumonia, UTI, sepsis)
L - Lifestyle excess (salt/fluid excess, alcohol)
U - Uraemia / Volume overload (renal failure)
R - Raised BP (hypertensive emergency) / RV failure (PE)
E - Embolism (pulmonary embolism) / Endocarditis

---

PATHOGENESIS / ETIOPATHOGENESIS

Neurohormonal Model (Central Concept)

INITIAL MYOCARDIAL INJURY / DYSFUNCTION
              |
         ↓ Cardiac Output
              |
    __________|_________________________
    |                                  |
BARORECEPTOR                    MACULA DENSA
ACTIVATION                      (↓ Renal perfusion)
    |                                  |
↑ SNS activation                  ↑ RENIN release
    |                                  |
Norepinephrine ↑              Angiotensin I → II
    |                                  |
 ___↓____________                 _____|__________
 |         |    |                 |     |        |
↑HR    Vasocon- ↑Renin           ↑SVR  Aldoster- ADH
       striction                       one      (AVP)
           |                      |     |        |
           |                      |  Na+/H2O   H2O
           |                      |  retention  retention
           |________________________|____________|
                         |
                ↑ Preload + Afterload
                ↑ Blood Volume
                         |
              Initially compensatory
                         |
              CHRONICALLY MALADAPTIVE
                         |
         ________________________
         |                      |
   Cardiac Remodeling      Congestion
   - Hypertrophy            Symptoms
   - Dilatation
   - Fibrosis
   - Apoptosis
         |
   Further ↓ EF
         |
   Vicious cycle of worsening HF

Compensatory Mechanisms (Initially Helpful, Later Harmful)

---

CLASSIFICATION OF CHF

1. By Left Ventricular Ejection Fraction (EF) - MOST IMPORTANT

HEART FAILURE CLASSIFICATION BY LVEF
              |
    __________|_______________________________________________
    |                    |                                 |
HFrEF                HFmrEF                            HFpEF
(Reduced EF)         (Mildly Reduced)               (Preserved EF)
    |                    |                                 |
LVEF < 40%          LVEF 41-49%                     LVEF ≥ 50%
"Systolic HF"        (Gray Zone)                  "Diastolic HF"
    |                    |                                 |
RCT evidence-       Limited evidence              Structural/
based therapy                                     functional
proven                                            abnormality
                                                  needed

2. ACC/AHA Staging vs NYHA Functional Classification

3. By Side of Failure

LEFT HEART FAILURE          RIGHT HEART FAILURE
↓ LV output                 ↓ RV output
↑ LAP → ↑ PCWP             ↑ RAP → ↑ JVP
Pulmonary congestion        Systemic congestion
↓ Exercise tolerance        Peripheral oedema
Orthopnoea, PND             Hepatomegaly, ascites
Causes:                     Causes:
- CAD, HTN, AS, AR, MR      - Pulmonary HTN
- DCM                       - Left HF (most common)
                            - COPD (Cor pulmonale)
                            - PE

4. By Onset: Acute vs Chronic HF

5. By Output: Low Output (most common) vs High Output HF

---

CLINICAL FEATURES

Symptoms

Left Heart Failure Symptoms

1. Dyspnoea on exertion (DOE) - earliest & most common
2. Orthopnoea - dyspnoea on lying flat; grade in pillows
3. Paroxysmal Nocturnal Dyspnoea (PND) - wakes from sleep, relieved on sitting up
4. Cardiac Asthma - wheeze due to bronchospasm from pulmonary oedema
5. Cheyne-Stokes respiration - cyclic crescendo-decrescendo breathing with apnoeic episodes (severe HF, low CO)
6. Fatigue and weakness - low cardiac output
7. Nocturia - improved renal perfusion in supine position

Right Heart Failure Symptoms

1. Ankle swelling (oedema)
2. Right hypochondrial pain/discomfort (hepatomegaly)
3. Abdominal distension (ascites)
4. Anorexia, nausea (bowel oedema / hepatic congestion)

Signs

CLINICAL SIGNS OF CHF
              |
    __________|__________________________
    |                                   |
LEFT HF SIGNS                     RIGHT HF SIGNS
    |                                   |
Pulse: Tachycardia,               JVP elevated (>4cm)
Pulsus alternans                  Abdominojugular reflex
(↑ JVP with abdominal
 compression)
BP: Low pulse pressure            Peripheral pitting
Apex: Displaced, diffuse          oedema (ankle, sacrum)
Auscultation:                     Hepatomegaly (tender,
- S3 gallop (volume overload,     pulsatile in TR)
  low EF = ventricular diastole)  Ascites
- S4 gallop (stiff ventricle,     Pleural effusion
  HFpEF, HTN)                     (typically R > L)
Lung crepitations (basal)         Splenomegaly (portal HTN)
Wheeze                            Jaundice (cardiac cirrhosis)

Key Physical Signs Summary

---

DIAGNOSIS

Investigations

DIAGNOSTIC WORK-UP FOR CHF
          |
    ______|___________________________________
    |          |           |         |       |
CLINICAL    ECG        CHEST     ECHO    BLOOD
    |          |          X-RAY       |    TESTS
    |       LVH/         ABCDE    Gold      |
(Framingham   Bundle     Mnemonic Standard  BNP/NT-proBNP
  criteria)   block                         Urea/Creat
             Ischaemia                      LFTs
             Arrhythmia                     TFT
             Poor R                         FBC
             progression                    HbA1c

Chest X-Ray - "ABCDE" Features of CHF

A - Alveolar oedema (bat-wing/butterfly perihilar haziness)
B - Kerley B lines (horizontal lines at bases = interstitial oedema)
C - Cardiomegaly (CTR > 0.5)
D - Dilated upper lobe vessels (redistribution - "cephalization")
E - Effusion (pleural - typically bilateral, R > L)

Echocardiography (2D + Doppler) - GOLD STANDARD

Biomarkers

Framingham Criteria (Clinical Diagnosis)

• PND or orthopnoea
• Neck vein distension
• Rales / Pulmonary oedema on X-ray
• S3 gallop
• Cardiomegaly
• Acute pulmonary oedema
• Weight loss >4.5 kg in 5 days on Rx

• Bilateral ankle oedema
• Nocturnal cough
• DOE
• Hepatomegaly
• Pleural effusion
• Tachycardia (>120 bpm)
• Decrease in vital capacity by 1/3

---

MANAGEMENT OF CHF

Acute Decompensated HF (ADHF) - Emergency Management

ACUTE PULMONARY OEDEMA / ADHF
          |
  O - Oxygen: Target SpO2 >94%
              CPAP/BiPAP (NIV) if severe
              Intubation if unresponsive
          |
  P - Position: Sit upright (↓ preload)
  O - Opiates: Morphine 2-4mg IV (↓ anxiety, vasodilates)
  N - Nitrates: IV GTN infusion (potent preload/afterload reduction)
              AVOID if SBP <90 mmHg
  D - Diuretics: IV Furosemide 40-80mg IV STAT
                 (Venodilator + diuretic effect)
              If refractory: Bumetanide, Torsemide, Metolazone combo
          |
  Identify & Treat Precipitant:
  - AF: Rate control / Cardioversion
  - Hypertensive emergency: IV nitrates / hydralazine
  - PE: Anticoagulation
  - Sepsis: Antibiotics
          |
  If Haemodynamically Unstable (SBP <90):
  - Inotropes: Dobutamine (beta-1 agonist)
  - Vasopressors: Noradrenaline if vasodilatory shock
  - Mechanical support: IABP, Impella, LVAD
  - Vasopressin antagonists: Tolvaptan (hyponatraemia)

Chronic HF Management - HFrEF

The "Fantastic Four" (4 Pillars of HFrEF Treatment - 2024 Guidelines)

ALL HFrEF PATIENTS SHOULD RECEIVE:
          |
    ______|_________________________________________
    |           |             |                   |
ARNI/ACEi/ARB  BETA-BLOCKER  MRA           SGLT2 INHIBITOR
(Sacubitril/   (Carvedilol/  (Spironolac-  (Dapagliflozin/
 Valsartan      Bisoprolol/   tone/          Empagliflozin
 PREFERRED)     Metoprolol    Eplerenone)    10mg OD)
    |           succinate)        |               |
PARADIGM-HF   ↓ mortality   RALES/EMPHA-   DAPA-HF/
trial: 20%    by 34-35%     SIS trials     EMPEROR-R:
↓ mortality                               ↓ HF hospitali-
vs enalapril                              sation by 26%
    |           |              |               |
   ↓SVR      ↓ Remodelling  ↓ K+, Fibrosis   ↓ Volume
   ↓ Fibrosis               ↓ Aldosterone    Cardiorenal
                                              protection

Management Algorithm - HFrEF

HFrEF (LVEF < 40%) - Symptomatic
          |
STEP 1: Start "Fantastic Four" at low doses
- ARNI (Sacubitril/Valsartan) or ACEi/ARB
- Beta-blocker (Carvedilol 3.125mg BD / Bisoprolol 1.25mg OD)
- Spironolactone 25mg OD (if K+ < 5.0)
- Dapagliflozin 10mg OD / Empagliflozin 10mg OD
- Add Loop diuretic for symptom relief (NOT proven mortality benefit)
          |
STEP 2: Titrate to maximum tolerated doses over weeks
          |
STEP 3: Reassess in 3-6 months
          |
Still symptomatic (NYHA II-III) + LVEF ≤35%?
          |
DEVICE THERAPY:
- ICD: LVEF ≤35% despite 3 months optimal therapy
        (MADIT-II, SCD-HeFT trials)
- CRT (Cardiac Resynchronization Therapy):
        LVEF ≤35% + QRS ≥150ms (LBBB morphology)
        NYHA II-IV
        (CARE-HF, COMPANION trials)
- CRT-D: Both ICD + CRT
          |
STEP 4: Refractory / End-stage HF (Stage D)
- Cardiac transplantation (Gold standard)
- LVAD (Left Ventricular Assist Device) - bridge to transplant
        or destination therapy
- Ivabradine: If sinus rhythm + HR ≥75 + on max beta-blocker
              (SHIFT trial: ↓ HF hospitalisation)
- Vericiguat (sGC stimulator): Recent hospitalisation for HFrEF
- Digoxin: Rate control in AF + HF; symptom benefit (no mortality benefit)

Drug Summary - HFrEF

Management of HFpEF (LVEF ≥ 50%)

HFpEF MANAGEMENT (Limited evidence vs HFrEF)
          |
Treat underlying cause:
- Control HTN (main driver)
- Rate control in AF
- Revascularise if ischaemia
- Manage DM, Obesity
          |
SGLT2 inhibitors:
- Dapagliflozin (DELIVER trial): ↓ CV death + HF hosp
- Empagliflozin (EMPEROR-P trial): ↓ HF hospitalisation
(BOTH now recommended for HFpEF - 2023 guidelines)
          |
Symptom control:
- Diuretics (furosemide) for fluid overload
- Verapamil/Beta-blocker for AF rate control
- Spironolactone (TOPCAT trial - borderline benefit)
- ARB (Candesartan - CHARM Preserved: modest benefit)

---

Q.27 - RECENT ADVANCES IN INVESTIGATION & TREATMENT OF CAD (20 Marks)

---

PART A: RECENT ADVANCES IN INVESTIGATION OF CAD

Overview

INVESTIGATIONS IN CAD
          |
    ______|_____________________________
    |               |                 |
NON-INVASIVE    INVASIVE          MOLECULAR/
IMAGING         INVESTIGATIONS    BIOMARKERS
    |               |                 |
- ECG             ICA + FFR         hsTroponin
- Exercise         IVUS              LP(a)
  treadmill        OCT               CRP
- Stress echo      NIRS              Genetic risk
- Nuclear MPI      PressureWire
- Cardiac CT       iFR
  (CCTA / FFR-CT)
- Cardiac MRI

---

1. Coronary CT Angiography (CCTA)

• Visualizes LUMEN + WALL (plaque characterisation)
• High negative predictive value (>97%) - excellent to RULE OUT CAD
• Can detect vulnerable/high-risk plaques (positive remodelling, low attenuation plaque)

• Low attenuation plaque (<30 HU - lipid rich)
• Positive remodelling
• Napkin ring sign
• Spotty calcification

---

2. FFR-CT (Fractional Flow Reserve from CT)

CTA Anatomy + Computational Fluid Dynamics
             |
    Simulated Blood Flow under Maximal Hyperaemia
             |
    FFR-CT value calculated for each vessel lesion
             |
    FFR-CT > 0.80 = Hemodynamically INSIGNIFICANT
    FFR-CT ≤ 0.80 = Hemodynamically SIGNIFICANT
             |
    PLATFORM trial: FFR-CT guided approach led to 61% 
    cancellation of ICA procedures without adverse events
    + Lower cost + Better QoL

---

3. Cardiac MRI (CMR)

• Gold standard for myocardial viability assessment (LGE)
• Distinguishes ischaemic from non-ischaemic aetiology
• Assesses myocardial perfusion (stress CMR) - equal to nuclear MPI
• No radiation, no iodinated contrast
• Mapping techniques (T1, T2, ECV mapping) for myocardial characterization

• Sub-endocardial LGE: Ischaemic pattern (follows coronary territory)
• LGE > 50% wall thickness: Non-viable, revascularisation unlikely to help
• No LGE: Hibernating/stunned myocardium - likely to recover

---

4. Invasive Coronary Angiography (ICA) + Physiological Assessment

Conventional Coronary Angiography

• Still gold standard for anatomical assessment
• Limitation: Only visualizes lumen, not plaque

FFR (Fractional Flow Reserve)

CONCEPT OF FFR
Myocardial FFR = Pd/Pa during maximal hyperaemia
                 (Adenosine)
         |
Pd = Distal coronary pressure
Pa = Proximal aortic pressure
         |
FFR >0.80 = Functionally INSIGNIFICANT
         (Defer revascularisation)
FFR ≤0.80 = Functionally SIGNIFICANT
         (Revascularise)
         |
DEFER trial: FFR >0.75 deferred lesions - 5yr MACE same as revascularised
FAME trial: FFR-guided PCI vs angio-guided → ↓ MACE at 1 year
FAME-2 trial: FFR ≤0.80 → PCI superior to medical therapy

iFR (Instantaneous Wave-Free Ratio)

• Pressure ratio in wave-free period (diastole) WITHOUT adenosine
• Cut-off: ≥0.89 = defer, <0.89 = revascularise
• Non-inferior to FFR (DEFINE-FLAIR, iFR-SWEDEHEART trials)
• Advantage: No adenosine side effects (flushing, bradycardia, bronchospasm)

---

5. Intracoronary Imaging

IVUS (Intravascular Ultrasound)

• Tomographic imaging of vessel wall and plaque
• Used for: Stent sizing, optimization, LM assessment, plaque characterization
• Limitation: Cannot see within plaque (lipid pool)

OCT (Optical Coherence Tomography)

• Near-infrared light; 10x higher resolution than IVUS
• Best for: Thin-cap fibroatheroma (TCFA) detection, stent strut apposition, plaque erosion vs rupture
• Limitation: Requires blood clearance (saline flush), limited penetration depth

NIRS (Near-Infrared Spectroscopy)

• Detects lipid-core plaques (yellow plaque = TCFA)
• Predicts future MACE from non-culprit lesions (PROSPECT II trial)

---

6. Advanced Biomarkers

---

PART B: RECENT ADVANCES IN TREATMENT OF CAD

1. Antiplatelet Therapy Advances

Newer P2Y12 Inhibitors

Aspirin-Free Strategies

• P2Y12 monotherapy after brief dual antiplatelet (1-3 months DAPT then drop aspirin): TWILIGHT, TICO trials
• Reduces bleeding without increasing ischaemic events in selected patients

Colchicine

• LoDoCo2 / COLCOT trials: Colchicine 0.5mg OD in chronic/post-MI CAD
• Reduces MACE by 23-31% through anti-inflammatory mechanism
• Now guideline-recommended as adjunct (2024 ESC guidelines)

---

2. Percutaneous Coronary Intervention (PCI) Advances

ADVANCES IN PCI
          |
    ______|_________________________
    |           |         |       |
STENT        IMAGING    PHYSIO-  COMPLEX
TECHNOLOGY   GUIDED     LOGICAL  LESION
    |         PCI        PCI     TECHNIQUES
    |           |         |         |
DES 3rd      IVUS/      FFR/    Rotational
generation   OCT:       iFR     atherectomy
(Zotarolimus  Reduces    guided  (calcified)
Everolimus)   MACE vs           Orbital
              angio-            atherectomy
Bioresorbable guided            IVUS-guided
Vascular      (ILUMIEN            LM PCI
Scaffold      OCST3 trial)      CTO-PCI
(BVS - in dev)

Bioresorbable Vascular Scaffold (BVS)

• Polymer scaffold that degrades over 2-3 years leaving no permanent metal
• Concept: "Leaves nothing behind"
• Current status: Early generation had issues (late scaffold thrombosis); new generations in development

Left Main (LM) PCI

• EXCEL trial: PCI non-inferior to CABG for LM disease at 3 years
• NOBLE trial: CABG superior at 5 years
• Current: Heart Team decision; PCI acceptable for SYNTAX score ≤22

CTO-PCI (Chronic Total Occlusion)

• Antegrade + retrograde crossing techniques
• Improves angina, LVEF; no proven mortality benefit
• Requires specialized operators

---

3. Coronary Artery Bypass Grafting (CABG) Advances

• Total arterial revascularisation: Bilateral internal mammary artery (BIMA) + radial artery grafts
  • BIMA: Better long-term patency vs single IMA + SVG
  • BIMA grafting: 95% 10-year patency vs 60% for SVG
• Off-pump CABG (OPCAB): Without cardiopulmonary bypass - reduces atrial fibrillation, stroke, renal failure
• Minimally invasive CABG (MIDCAB): Via small left anterolateral thoracotomy
• Hybrid revascularisation: MIDCAB for LAD + PCI for non-LAD lesions
• Robotic-assisted CABG: Total endoscopic CABG

---

4. Pharmacological Advances

PCSK9 Inhibitors

• Drugs: Evolocumab (Repatha), Alirocumab (Praluent)
• Mechanism: Monoclonal antibodies blocking PCSK9 → ↑ LDL-R expression → ↓ LDL
• Trials: FOURIER (Evolocumab), ODYSSEY (Alirocumab) - both ↓ LDL by 50-60% ON TOP of statin, ↓ MACE
• Inclisiran: Small interfering RNA (siRNA) against PCSK9 - twice yearly injection (ORION trials)
• Indication: Very high-risk patients, familial hypercholesterolaemia, statin-intolerant

Icosapent Ethyl (Vascepa)

• Highly purified EPA (omega-3 fatty acid)
• REDUCE-IT trial: ↓ MACE by 25% in high-risk patients with ↑ TG despite statin

Colchicine (as above)

Empagliflozin / Dapagliflozin in CAD + HF

• Cardioprotective beyond glucose lowering

---

5. Coronary Physiology Advances

RFR (Resting Full-cycle Ratio)
DFR (Diastolic Pressure Ratio)
CFR (Coronary Flow Reserve)
IMR (Index of Microcirculatory Resistance)
      |
Combined physiology assessment (FFR + IMR):
- Identifies both epicardial and microvascular disease
- COMFORTABLE AMI trial: Microvascular obstruction
  (IMR > 40) = worse outcomes post-STEMI

---

6. Transcatheter Procedures

• TAVI/TAVR: Not directly CAD, but often accompanies
• Renal Denervation: For resistant hypertension (indirect CAD risk reduction)
  • RADIANCE II, SPYRAL HTN-OFF MED trials: Significant BP reduction

---

7. Cardiac Rehabilitation & Digital Health

• Structured exercise-based cardiac rehab post-MI: ↓ mortality 26%, ↓ reinfarction
• Wearable ECG devices (Apple Watch, KardiaMobile): Detect AF early in CAD patients
• Remote patient monitoring: Home BP + weight sensors for HF/CAD
• AI-assisted image analysis: Automated CCTA stenosis grading

---

DRUG SHORT ANSWERS

---

DRUG 1: ARNI (Angiotensin Receptor Neprilysin Inhibitor)

Agent: Sacubitril/Valsartan (Entresto)

Mechanism

SACUBITRIL/VALSARTAN
          |
    ______|_____________
    |                  |
SACUBITRIL             VALSARTAN
(Neprilysin inhibitor  (ARB - AT1 receptor blocker)
prodrug, activated     |
by esterases)          Blocks Angiotensin II
    |                  |
Inhibits neprilysin    ↓ Vasoconstriction
(endopeptidase that    ↓ Aldosterone
breaks down ANP,       ↓ Na/H2O retention
BNP, adrenomedullin,       |
bradykinin)                ↓ Preload + Afterload
    |
↑ ANP/BNP levels
↑ Adrenomedullin
(Combined effect:)
    |
↑ Natriuresis + Diuresis
↑ Vasodilation
↓ Sympathetic activity
↓ Cardiac hypertrophy and fibrosis
↓ RAAS activation

Pharmacokinetics

• Oral, twice-daily dosing (doses: 24/26mg, 49/51mg, 97/103mg BD)
• Sacubitril: Half-life ~10h, renal excretion
• Valsartan: Half-life ~10h, fecal excretion

Clinical Evidence

• PARADIGM-HF Trial (n=8442): Sacubitril/valsartan vs enalapril in HFrEF
  • ↓ CV death by 20%
  • ↓ HF hospitalisation by 21%
  • ↓ All-cause mortality by 16%
  • Trial stopped early for clear benefit

Indications

1. HFrEF (LVEF <40%), NYHA class II-IV - First-line preferred over ACEi/ARB
2. Recently hospitalised for HF (can be started in hospital)
3. HFpEF (LVEF ≥50%) - PARAGON-HF: Borderline benefit, especially in women/LVEF 45-55%

Key Rules

1. MUST stop ACEi ≥36 hours before starting (angioedema risk - both ACEi and neprilysin inhibit bradykinin degradation)
2. Never combine with ACEi (only with ARB)
3. If switching from ARB: Can switch directly (no washout)
4. Check BP: SBP should be ≥95 mmHg before starting
5. Neprilysin raises BNP → Use NT-proBNP for monitoring (not BNP)

Adverse Effects

Contraindications

1. History of hereditary/ACEi-associated angioedema
2. Concomitant ACEi use (or within 36h)
3. Bilateral RAS
4. Pregnancy
5. SBP <95 mmHg

---

DRUG 2: DIGOXIN

Quick Summary

---

DRUG 3: NEPRILYSIN INHIBITOR

Neprilysin Overview

• Zinc-dependent metalloprotease on cell membranes
• Present in: Kidney (proximal tubule), lung, heart, brain, neutrophils

Substrates Degraded by Neprilysin

NEPRILYSIN degrades:
    |
    |_________________________________
    |           |          |         |
  ANP/BNP  Bradykinin  Adrenomedullin  Angiotensin II
    |                                         |
Vasodilatory/                            Vasoconstrictive
Natriuretic                              (therefore MUST combine
(inhibition = GOOD                       neprilysin inhibitor with
for HF)                                  RAAS blocker)

Why Neprilysin Inhibition Alone is Insufficient

• Pure neprilysin inhibition (e.g., Candoxatril) also raises Ang II → hypertension
• Must always combine with RAAS blocker
• ACEi + Neprilysin inhibitor (Omapatrilat) = ↑↑↑ Bradykinin → 3x more angioedema (IMPRESS, OVERTURE trials) → FAILED
• Solution: ARB + Neprilysin inhibitor = ARNI (Sacubitril/Valsartan) - much lower angioedema risk

Effects of Neprilysin Inhibition

Clinical Application

• Sacubitril is the only approved neprilysin inhibitor (as part of ARNI)
• BNP elevated with sacubitril → Use NT-proBNP for monitoring
• Reduces LVEDP, pulmonary capillary wedge pressure, heart rate
• Improves cardiac remodelling (↓ LV volumes, ↑ LVEF over time)

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DRUG 4: ANTIARRHYTHMIC DRUGS IN MANAGEMENT OF UNSTABLE ANGINA (UA)

Context: Why Antiarrhythmics in UA?

• Non-obstructive coronary disease or severe stenosis with plaque erosion
• Associated with myocardial ischaemia → triggers arrhythmias (AF, VT, VF)
• Arrhythmias in UA increase morbidity and mortality

Classification of Antiarrhythmic Drugs (Vaughan Williams)

Role of Antiarrhythmic Drugs in UA

1. BETA-BLOCKERS (Class II) - FIRST LINE in UA

BETA-BLOCKERS IN UA
          |
Mechanism: ↓ Heart rate, ↓ contractility
           ↓ Myocardial O2 demand
           ↓ SNS activation
           ↑ Diastolic filling time → better coronary perfusion
           Anti-arrhythmic (↓ AF, VT risk)
          |
Drug: Metoprolol (IV 5mg q5min x3 then oral)
      Atenolol, Bisoprolol, Carvedilol
          |
Evidence: Reduce VF/sudden death in UA/NSTEMI
Guideline recommendation: Class I indication
          |
CONTRAINDICATIONS:
- Severe bradycardia (HR <50)
- AV block (2nd/3rd degree)
- Active bronchospasm/severe asthma
- Acute decompensated HF (use cautiously)
- Cocaine-induced ACS (risk of unopposed alpha - use benzodiazepine)

2. LIGNOCAINE (Lidocaine) - Class Ib

Used for: VT/VF in UA/NSTEMI setting
Mechanism: Fast Na+ channel blocker
           Preferred in ischaemic myocardium (binds ischaemic cells)
           Shortens action potential duration
Dose: IV bolus 1-1.5 mg/kg then infusion 1-4 mg/min
Use: No longer routine prophylaxis (IMPACT trial: No mortality benefit,
     ↑ asystole)
     Still used for acute VT/VF when amiodarone unavailable

3. AMIODARONE (Class III) - Broad Spectrum

AMIODARONE IN UA
          |
Mechanism: Multi-channel blocker
           - Na+ channel (Ib-like)
           - K+ channel (main)
           - Ca++ channel
           - Beta-receptor (non-competitive)
           Prolongs QT, QRS, PR
          |
Indications in UA:
- Atrial Fibrillation with rapid ventricular rate
- Ventricular tachycardia / VF (after failed defibrillation)
- Rate control when beta-blockers contraindicated
          |
Dose in Emergency:
- VT/VF: 300mg IV bolus (then 900mg over 24h)
- AF rate control: 5mg/kg IV over 1h then 50mg/h infusion
          |
Side effects: Phlebitis (IV), hypotension, bradycardia
Long-term: Pulmonary fibrosis, thyroid toxicity, corneal deposits,
           hepatotoxicity, photosensitivity

4. VERAPAMIL / DILTIAZEM (Class IV) - Non-DHP CCBs

Role in UA:
- Rate control in AF when beta-blockers contraindicated
- Anti-anginal: ↓ HR + vasodilation
          |
IMPORTANT CONTRAINDICATION:
- NEVER use non-DHP CCB in HF (↓ contractility worsens HF)
- NEVER combine with beta-blocker (complete AV block risk)
- NOT for routine arrhythmia prophylaxis in ACS

5. ADENOSINE (Class V)

• Used for SVT (AVNRT/AVRT) complicating UA
• Rapidly terminates narrow complex SVT
• Half-life: 10-15 seconds
• Dose: 6mg IV bolus → 12mg if no response
• Avoid in: AF/Flutter (may cause VF in WPW), Asthma

Summary: Antiarrhythmics in UA Context

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QUICK REFERENCE SUMMARY TABLE

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Sources: Goldman-Cecil Medicine (9780323930345); Fuster & Hurst's The Heart 15th Ed (9781264257560); Braunwald's Heart Disease (9780323722193); Lippincott Pharmacology (9781975170561); Katzung's Basic & Clinical Pharmacology 16e (9781260463309); Harrison's Principles 22E (9781265977061)