19.1 Valvular Heart Disease, CAD & Cardiopulmonary Bypass Management

19.1 Valvular Heart Disease, CAD & Cardiopulmonary Bypass Management

Cardiac anesthesia for the Certified Registered Nurse Anesthetist (CRNA) demands mastery of valvular pathophysiology, coronary perfusion dynamics, and the non-physiologic state of cardiopulmonary bypass (CPB). Anesthesia providers must tailor inotropes, vasopressors, fluid administration, and ventilatory parameters to match specific pressure-volume relationships and preserve myocardial oxygen supply-demand balance.

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1. Valvular Heart Disease Hemodynamics: The Master Framework

Valvular lesions are classified by their primary hemodynamic insult: pressure overload (stenosis) versus volume overload (regurgitation), and their anatomical location (aortic versus mitral).

+--------------------------------------------------------------------------------------------------------------------+
|                                MASTER VALVULAR HEMODYNAMIC MANAGEMENT MATRIX                                       |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+
| Valvular Lesion       | Primary Remodeling  | Heart Rate Goal   | Preload Goal        | Afterload (SVR) Goal       |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+
| **Aortic Stenosis**   | Concentric LVH      | **Slow-Normal**   | **High / Full**     | **Maintained / High**      |
| (AS)                  | (Pressure Overload) | (60 - 70 bpm)     | (Fills stiff LV)    | (Preserves DBP and CPP)    |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+
| **Aortic Regurg**     | Eccentric LVH       | **Fast**          | **Full**            | **Low / Decreased**        |
| (AR)                  | (Volume Overload)   | (80 - 100 bpm)    | (Maintains forward) | (Reduces regurg fraction)  |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+
| **Mitral Stenosis**   | LA Dilation & RVH   | **Slow**          | **Normal / Full**   | **Maintained**             |
| (MS)                  | (LA Pressure ↑)     | (60 - 70 bpm)     | (Fills LV in diast) | (Avoid PVR triggers!)      |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+
| **Mitral Regurg**     | Eccentric LVH & LA  | **Fast**          | **Full**            | **Low / Decreased**        |
| (MR)                  | (Volume Overload)   | (80 - 100 bpm)    | (Maintains forward) | (Promotes aortic ejection) |
+-----------------------+---------------------+-------------------+---------------------+----------------------------+

Aortic Stenosis (AS)

• Anatomy & Severity: Normal aortic valve area (AVA) is $3.0 - 4.0 \text{ cm}^2$. Severe AS is defined as $\text{AVA} < 1.0 \text{ cm}^2$ (indexed AVA $< 0.6 \text{ cm}^2/\text{m}^2$), mean transvalvular gradient $> 40 \text{ mmHg}$, or peak jet velocity $> 4.0 \text{ m/s}$.
• Pathophysiology: Chronic pressure overload forces the left ventricle to generate transvalvular systolic pressures exceeding $200 - 250 \text{ mmHg}$, inducing concentric left ventricular hypertrophy (LVH) (sarcomeres added in parallel, thickened wall, reduced LV compliance). High intracavitary pressure increases myocardial wall tension ($T = \frac{P \times r}{2h}$) and dramatically elevates myocardial oxygen demand ($MVO_2$).
• Diastolic Filling & Atrial Kick: The stiff, non-compliant LV is critically dependent on late diastolic active filling ("atrial kick"), which contributes up to $30 - 40%$ of stroke volume. Sudden loss of sinus rhythm (e.g., atrial fibrillation or junctional rhythm) causes instantaneous hemodynamic collapse.
• Hemodynamic Rules:
  • Heart Rate (60-70 bpm): Tachycardia shortens diastole (the only time the subendocardium is perfused) and increases $MVO_2$. Severe bradycardia ($<50 \text{ bpm}$) cannot be compensated by an increase in stroke volume because stroke volume is fixed across the stenotic orifice.
  • Rhythm: Maintain normal sinus rhythm at all times. Cardiovert new-onset atrial fibrillation immediately.
  • Preload: High-normal. Hypovolemia causes severe underfilling of the stiff LV, resulting in precipitous hypotension.
  • Afterload (SVR): Maintain high-normal SVR. Vasodilation drops diastolic blood pressure (DBP), collapsing coronary perfusion pressure ($CPP = DBP - LVEDP$). Phenylephrine is the vasopressor of choice; avoid spinal or rapid epidural boluses.

Aortic Regurgitation (AR)

• Pathophysiology: Incompetent aortic valve leaflets allow retrograde regurgitation of blood from the aorta into the LV during diastole. This creates chronic combined volume and pressure overload, resulting in eccentric LV hypertrophy (sarcomeres added in series, massive chamber dilation, "cor bovinum"). The stroke volume is split into forward stroke volume and backward regurgitant volume. Pulse pressure is markedly widened (e.g., $160/40 \text{ mmHg}$), with rapid arterial collapse (water-hammer / Corrigan pulse).
• The Regurgitant Fraction Formula: $\text{Regurgitant Volume} \propto \text{Regurgitant Orifice Area} \times \sqrt{\text{Aortic-to-LV Diastolic Pressure Gradient}} \times \text{Diastolic Time}$
• Hemodynamic Rules ("Fast, Forward, Full"):
  • Heart Rate (80-100 bpm): Faster heart rates shorten diastole, directly decreasing the duration available for retrograde regurgitant flow.
  • Afterload (Decreased SVR): Vasodilation promotes forward aortic outflow into the systemic circulation and reduces retrograde flow back into the LV. Hydralazine, nitroprusside, or ACE inhibitors are beneficial.
  • Preload: Maintained/full to support augmented forward stroke volume.
  • Avoid: Bradycardia (prolonged diastole causes massive LV distension, elevated LVEDP, and acute pulmonary edema) and elevated afterload (forces blood back through the aortic valve).

Mitral Stenosis (MS)

• Pathophysiology: Most commonly caused by rheumatic heart disease. Normal mitral valve area (MVA) is $4.0 - 5.0 \text{ cm}^2$. Severe MS occurs at $\text{MVA} < 1.5 \text{ cm}^2$ (critical MS $< 1.0 \text{ cm}^2$). Left ventricular inflow obstruction causes elevated left atrial pressure (LAP), progressive LA enlargement, and pulmonary venous congestion.
• Secondary Pulmonary Hypertension & Cor Pulmonale: Chronic elevated LAP triggers reactive pulmonary arteriolar vasoconstriction, pulmonary arterial hypertension (PAH), right ventricular hypertrophy (RVH), tricuspid regurgitation, and right heart failure.
• Hemodynamic Rules:
  • Heart Rate (60-70 bpm): Slow heart rate is vital. Diastolic filling across a stenotic mitral valve requires adequate time. Tachycardia drastically shortens diastolic filling, causing blood to back up into the pulmonary vasculature, precipitating acute flash pulmonary edema.
  • Rhythm: Maintain normal sinus rhythm. Loss of atrial kick combined with rapid ventricular response in atrial fibrillation is life-threatening.
  • Preload: Maintain normal intravascular volume. Overhydration causes acute pulmonary edema; dehydration severely starves the LV of preload.
  • Pulmonary Vascular Resistance (PVR): Strictly avoid triggers that increase PVR: hypoxemia ($PaO_2 < 60$), hypercapnia ($PaCO_2 > 45$), acidosis ($pH < 7.35$), hypothermia, nitrous oxide ($N_2O$), and sympathetic stimulation/pain.

Mitral Regurgitation (MR)

• Pathophysiology: Incompetent mitral valve allows systolic ejection into both the high-resistance aorta and the low-pressure left atrium. This creates volume overload of both the left atrium and left ventricle, leading to eccentric LVH and LA enlargement. Severe MR is characterized by a prominent systolic $v$ wave on pulmonary artery occlusion pressure (PAOP) tracings.
• Hemodynamic Rules ("Fast, Forward, Full"):
  • Heart Rate (80-100 bpm): Slightly elevated heart rate shortens the systolic ejection period and prevents excessive ventricular dilation.
  • Afterload (Decreased SVR): Reducing systemic vascular resistance facilitates forward LV ejection into the aorta and minimizes backward regurgitation into the compliant left atrium.
  • Preload: High-normal to optimize forward stroke volume.
  • Avoid: Acute increases in SVR (e.g., pure alpha-1 agonists like phenylephrine increase regurgitant fraction and worsen pulmonary edema) and bradycardia.

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2. Coronary Artery Disease & Myocardial Oxygen Balance

+---------------------------------------------------------------------------------------------------------+
|                         MYOCARDIAL OXYGEN SUPPLY VS. DEMAND EQUILIBRIUM                                 |
+----------------------------------------------------+----------------------------------------------------+
| Oxygen Supply Determinants                         | Oxygen Demand ($MVO_2$) Determinants               |
+----------------------------------------------------+----------------------------------------------------+
| 1. **Coronary Perfusion Pressure (CPP):**          | 1. **Heart Rate:** Most critical determinant!       |
|    • $CPP_{LV} = DBP - LVEDP$                      |    • Increases $MVO_2$ AND shortens diastolic supply|
|    • Left Ventricle perfused in **diastole only**  | 2. **Myocardial Wall Tension (Law of Laplace):**   |
|    • Right Ventricle perfused in **systole & diast**|    • $\sigma = \frac{P \times r}{2h}$               |
| 2. **Diastolic Time Fraction:**                    |    • Dependent on peak systolic pressure ($P$) and  |
|    • Shortened significantly by tachycardia        |      ventricular radius / preload ($r$)             |
| 3. **Arterial Oxygen Content ($CaO_2$):**          | 3. **Contractility ($dP/dt$):**                    |
|    • $CaO_2 = (Hgb \times 1.34 \times SaO_2) + (0.003 \times PaO_2)$| • Inotropic stimulation increases $MVO_2$|
| 4. **Coronary Vascular Resistance:**               | 4. **Basal Metabolic State:**                      |
|    • Autoregulation (MAP 60-140 mmHg) & tone       |    • Hypothermia decreases; shivering increases     |
+----------------------------------------------------+----------------------------------------------------+

$\mathbf{CPP_{\text{LV}} = \text{Diastolic Blood Pressure (DBP)} - \text{Left Ventricular End-Diastolic Pressure (LVEDP)}}$ $\mathbf{CPP_{\text{RV}} = \text{Aortic Mean Arterial Pressure (MAP)} - \text{Right Ventricular End-Diastolic Pressure (RVEDP)}}$

NCE Clinical Rule — LV vs. RV Perfusion Dynamics:

• The Left Ventricle is perfused almost exclusively during diastole because high intramyocardial tissue pressure during systole compresses intramural coronary vessels and halts subendocardial flow.
• The Right Ventricle is perfused during both systole and diastole because RV systolic intracavitary pressure ($25 \text{ mmHg}$) is significantly lower than aortic systolic pressure ($120 \text{ mmHg}$). However, in severe pulmonary hypertension with RV peak pressure equaling systemic pressure, RV perfusion becomes diastole-dependent, rendering the RV exquisitely vulnerable to ischemia.

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3. Cardiopulmonary Bypass (CPB): Circuit, Anticoagulation & Heparin Resistance

                    [THE EXTRACORPOREAL CARDIOPULMONARY BYPASS CIRCUIT]

         Right Atrium / Cavae  ===================>  Venous Reservoir
         (Deoxygenated Blood)   [Gravity / Vacuum]         |
                                                           v
                                                  Cardiotomy Suction
                                                  (Surgical Field Blood)
                                                           |
                                                           v
         Aortic Root / Ascending Aorta <=========== Main Arterial Pump
         (Oxygenated Blood to Body)    [Filter &]   (Roller or Centrifugal)
                                       [Heat Ex.]          |
                                                           v
                                                   Membrane Oxygenator
                                                   (Gas Exchange: O₂ / CO₂)

Systemic Heparinization Protocol

• Mechanism: Unfractionated heparin is a highly sulfated, negatively charged glycosaminoglycan (polyanion). It binds to Antithrombin III (ATIII), inducing a conformational change that accelerates ATIII's inhibition of thrombin (Factor IIa), Factor Xa, IXa, XIa, and XIIa by $1,000\text{-fold}$.
• Dosing: Administer $300 - 400 \text{ units/kg}$ IV through a secure central line prior to aortic cannulation.
• Target Activated Clotting Time (ACT):
  • Baseline ACT: $\approx 90 - 120 \text{ seconds}$.
  • Safe Cannulation ACT: $> 300 \text{ seconds}$.
  • Full Bypass ACT: $> 400 - 480 \text{ seconds}$ (measured 3-5 minutes after heparin administration and every 30 minutes on bypass).

Heparin Resistance & Antithrombin III Deficiency

• Definition: Failure to achieve an ACT $> 400 - 480 \text{ seconds}$ despite administering a total heparin dose of $400 - 600 \text{ units/kg}$.
• Etiology:
  1. Preoperative Heparin Therapy: Continuous IV heparin infusion in the ICU/CCU downregulates endogenous ATIII levels by $30 - 50%$.
  2. Congenital ATIII Deficiency: Rare autosomal dominant disorder.
  3. Acquired ATIII Deficiency: Sepsis, hepatic cirrhosis (decreased hepatic synthesis), nephrotic syndrome (urinary protein loss), DIC, hemodialysis.
• Treatment Protocol:
  1. Administer an additional heparin bolus ($100 - 200 \text{ units/kg}$).
  2. If ACT remains $< 400 \text{ seconds}$, administer Antithrombin III Concentrate ($500 - 1000 \text{ units}$ IV) or Fresh Frozen Plasma (FFP) ($2 - 4 \text{ units}$, each unit contains $\approx 200 - 250 \text{ units}$ of endogenous ATIII).

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4. Myocardial Protection: Cardioplegia Physiology

+---------------------------------------------------------------------------------------------------------+
|                                    CARDIOPLEGIA PHYSIOLOGIC CASCADE                                     |
+---------------------------------------------------------------------------------------------------------+
| 1. **Hyperkalemic Composition:** Extracellular potassium elevated to **15 - 30 mEq/L**                |
| 2. **Membrane Depolarization:** Resting membrane potential shifts from **-90 mV up to -50 mV**         |
| 3. **Fast Na⁺ Channel Inactivation:** Voltage-gated fast Na⁺ channels locked in inactive state          |
| 4. **Diastolic Arrest:** Phase 0 depolarization abolished → heart arrests in **flaccid diastole**       |
| 5. **Metabolic Suppression:** Arrest eliminates mechanical work, reducing $MVO_2$ by **>90%**           |
| 6. **Hypothermia (4°C):** Cold solution lowers myocardial temperature, reducing $MVO_2$ by **another 5%**|
+---------------------------------------------------------------------------------------------------------+

• Antegrade vs. Retrograde Delivery:
  • Antegrade: Delivered into the aortic root (or directly into coronary ostia if aortic cross-clamp applied). Relies on a competent aortic valve to push solution down native coronary arteries. Ineffective in severe aortic regurgitation.
  • Retrograde: Delivered into the coronary sinus via an inflatable balloon catheter placed through the right atrium. Perfusion flows retrogradely from cardiac veins back through the capillary bed. Ideal in severe AR or severe multivessel coronary artery occlusion.

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5. Weaning from Cardiopulmonary Bypass: The WARM Checklist

+-------------------------------------------------------------------------+
|                     WEANING FROM CPB: THE "WARM" CHECKLIST              |
+-------------------------------------------------------------------------+
|  **W** - **Warmth:** Normothermia achieved                              |
|         • Nasopharyngeal (core) temp: 36.5 - 37.0°C                     |
|         • Bladder / Rectal temp: > 35.5°C (prevents afterdrop & coag)   |
|                                                                         |
|  **A** - **Air Cleared & Anatomy:**                                     |
|         • TEE confirmation: Left ventricle, aortic root, & LA cleared   |
|         • Surgical vents turned off; cardiac chambers filled            |
|                                                                         |
|  **R** - **Rhythm & Rate:**                                             |
|         • Stable sinus rhythm or AV-sequential epicardial pacing        |
|         • Target rate: 70 - 90 bpm (avoids bradycardia & tachycardia)   |
|                                                                         |
|  **M** - **Monitoring, Metabolic, Mechanical & Medications:**           |
|         • **Mechanical Ventilation:** RESTARTED! 100% FiO₂, recruitment  |
|         • **Metabolic:** ABG normal, Hgb > 7.5-8 g/dL, K⁺ 4.0-5.0 mEq/L |
|         • **Medications:** Inotropes/vasopressors infused as indicated  |
+-------------------------------------------------------------------------+

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6. Protamine Sulfate Reversal & Adverse Reaction Subtypes

Protamine is a strongly basic, polycationic peptide purified from salmon sperm. When administered, positively charged protamine binds electrostatically to negatively charged heparin, forming an inert, stable salt precipitate without anticoagulant properties.

$\mathbf{Dosing: \quad 1.0 - 1.3 \text{ mg Protamine Sulfate per } 100 \text{ units of Heparin administered}}$

+---------------------------------------------------------------------------------------------------------+
|                                 CLASSIFICATION OF PROTAMINE ADVERSE REACTIONS                           |
+-------------------+------------------------------------+------------------------------------------------+
| Reaction Type     | Pathophysiologic Mechanism         | Clinical Signs & Management                    |
+-------------------+------------------------------------+------------------------------------------------+
| **Type I**        | • **Rapid Infusion (<10 mins)**    | • Systemic vasodilation, drop in SVR and MAP   |
| (Hypotension)     | • Direct histamine & bradykinin rel| • **Rx:** Slow infusion over 10-15 minutes,    |
|                   |   from tissue mast cells           |   IV fluid bolus, phenylephrine                |
+-------------------+------------------------------------+------------------------------------------------+
| **Type II**       | • **True Allergic / Anaphylactic** | • Urticaria, facial flushing, severe broncho-  |
| (Anaphylaxis /    | • IgE or IgG anti-protamine antibod|   spasm, catastrophic angioedema, shock        |
|  Anaphylactoid)   | • **High Risk:** Prior NPH insulin,| • **Rx:** Epinephrine, diphenhydramine,        |
|                   |   fish allergy, post-vasectomy     |   steroids, fluid resuscitation                |
+-------------------+------------------------------------+------------------------------------------------+
| **Type III**      | • **Catastrophic Pulmonary HTN**   | • Acute pulmonary vasoconstriction, massive    |
| (Pulmonary        | • Heparin-protamine complexes      |   rise in PAP and CVP, severe RV failure,      |
|  Vasoconstriction)|   trigger complement activation &  |   acute tricuspid regurgitation, LV collapse   |
|                   |   **Thromboxane A2 release**       | • **Rx:** Inhaled Nitric Oxide / Prostacyclin, |
|                   |                                    |   Milrinone, Vasopressin, re-institute CPB     |
+-------------------+------------------------------------+------------------------------------------------+

NCE Exam Trap — Protamine Cross-Reactivity: Patients with a history of NPH (Neutral Protamine Hagedorn) insulin usage have been chronically exposed to protamine and can develop circulating anti-protamine antibodies. Similarly, patients who have undergone a vasectomy develop cross-reacting antisperm antibodies because the disrupted blood-testis barrier exposes protamine in sperm nuclei to the systemic immune system. Both patient populations carry a significantly elevated risk of life-threatening Type II anaphylaxis and Type III pulmonary vasoconstriction upon protamine exposure.