B3W2 Trans Phys

Block 3 Week 2 Trans Review

Introduction to Heart Failure

• Functional Definition of Heart Failure (HF): A lifelong condition in which the heart muscle cannot pump enough blood to meet the body's oxygen needs.

  • Various subtypes of HF exist.

  • Currently no real cure; management is the primary approach.

Left Ventricular Function

• Left Ventricular (LV) Systolic Function:

  • Measure of how well the LV contracts to eject blood.

• Left Ventricular Ejection Fraction (LVEF):

  • Percentage of blood the LV ejects during systole.

  • Formula: LVEF = (Stroke Volume/End Diastolic Volume) x 100

  • Normal LVEF: > 50%

Epidemiology of Heart Failure

• Prevalence:

  • 2.3% of the population; roughly 6.7 million Americans.

  • Age is a significant risk factor; expected to rise to 3.0% by 2030.

• Mortality Rates:

  • 1-year mortality: ~29.6%.

  • 5-year mortality: ~52.3% (not improving).

• Economic Burden:

  • Significant costs compared to other chronic conditions; projected $70 billion by 2030.

Subtypes of Heart Failure by LVEF

• Heart Failure with Reduced Ejection Fraction (HFrEF):

  • LVEF < 40% (46% of HF cases).

• Heart Failure with Midrange Ejection Fraction (HFmrEF):

  • LVEF 41% to 49% (8% of HF cases).

• Heart Failure with Preserved Ejection Fraction (HFpEF):

  • LVEF > 50% (46% of HF cases).

Causes and Risk Factors for HFrEF

Common Causes:

• Hypertension, diabetes, obesity, smoking.

• Age over 65, male gender.

• Coronary artery disease and valvular issues.

Symptoms of HFrEF:

• Exercise intolerance

• Fatigue

• Palpitations

• Chest pain

Symptoms Severity Classification:

• Class I: No limitations in physical activity.

• Class II: Mild symptoms with moderate activity.

• Class III: Significant symptoms with light activity.

• Class IV: Symptoms at rest; any activity causes distress.

Mechanisms of HFrEF

Cardiac Insult and Function:

• Low stroke volume leads to reduced cardiac output.

• Volume overload leads to symptoms like dyspnea and peripheral edema.

RAAS Dysfunction:

• RAAS fails to compensate for low mean arterial pressure due to decreasing cardiac output.

  • Results in decreased muscle perfusion and promotes fibrosis.

Volume Overload:

• Kidneys retain fluid, worsening conditions due to RAAS activation.

Current Therapies for HFrEF

Main Approaches:

• Neurohormonal inhibition and symptom management are foundational.

  • RAAS Inhibition:

    • ACE inhibitors, ARBs, MRAs.

  • Fluid Management:

    • Use of diuretics.

  • Sympathetic System Support:

    • Beta-blockers to reduce heart workload and improve function.

Issues with Current Therapies:

• Adverse effects include hypotension, renal impairment, dizziness, electrolyte imbalances.

• Therapeutic strategies do not address the root cause of HFrEF.

Inotropic Therapy Overview

• Inotropic Agents: Therapies that increase myocardial contractility.

Mechanisms of Inotropic Agents:

• **β-adrenergic pathway **:

  • Majority manipulate this pathway to increase cardiac contractility.

• PDE Inhibitors: Prolong action of cAMP.

  • Past attempts resulted in higher mortality over long term.

Types of Inotropic Agents:

• β-Agonists (e.g., dobutamine):

  • Increase stroke volume but long-term use led to higher HF mortality.

• PDE Inhibitors (e.g., milrinone):

  • Similarly increased morbidity and mortality despite improved hemodynamics.

• Ca2+ Sensitizers (e.g., levosimendan):

  • Some positive outcomes but also risk of arrhythmias.

• Myosin Activators (e.g., omecamtiv mecarbil):

  • Newer agents that stabilize cardiac contractions but still face efficacy issues.

Future Considerations for Inotropic Therapy

• Need more effective approaches focusing on direct manipulation of cardiac contractility mechanisms.

• Explore synergies with other therapies targeting different HF pathways.

  • Such as metabolism, fibrosis, inflammation, etc.

• Continued clinical trials to further understand patient-specific benefits.