Heart Failure: Neurohormonal Model

Heart Failure

• Heart failure (HF) is a progressive clinical syndrome resulting from the heart's inability to pump sufficient blood to meet the body's metabolic needs.

Neurohormonal Model of Heart Failure

• The neurohormonal model is the current paradigm for understanding heart failure.
• Initiating events lead to decreased cardiac output, becoming a progressive systemic disease mediated by neurohormones and autocrine/paracrine factors.
• Drug therapies that target neurohormonal imbalances slow disease progression but do not stop it.

Neurohormones and Autocrine/Paracrine Factors

• Neurohormones involved in heart failure include angiotensin II, norepinephrine, aldosterone, and natriuretic peptides (ANP, BNP, and CNP).
• Autocrine/paracrine factors include proinflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β), which have negative inotropic effects, reduce β-receptor-mediated responses, increase myocardial cell apoptosis, and stimulate remodeling.

Heart Failure Exacerbation

• Heart failure exacerbation occurs when previously compensated patients develop worsening symptoms that require hospitalization.
• Factors that exacerbate heart failure include noncompliance with medications and dietary recommendations, cardiac events, non-cardiac events, and inadequate or inappropriate medications.
• Most causes of heart failure exacerbation are preventable.

Drugs that Exacerbate Heart Failure

• Certain drugs can exacerbate heart failure, including:
• Negative inotropic effect drugs: antiarrhythmics, β-blockers, calcium channel blockers, and cardiotoxic drugs (e.g., doxorubicin and trastuzumab).
• Sodium and water retention drugs: nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, thiazolidinediones, glucocorticoids, androgens, estrogens, and sodium-containing drugs.

Clinical Presentation

• Patient presentation may range from asymptomatic to cardiogenic shock, with symptoms including dyspnea, orthopnea, paroxysmal nocturnal dyspnea, chest pain, pulmonary edema, fatigue, nocturia, and confusion.

Factors Affecting Prognosis

• Factors affecting prognosis in heart failure include age, gender, left ventricular ejection fraction, renal function, extent of underlying coronary artery disease, diabetes, anemia, blood pressure, and heart failure etiology.

Etiology

• Heart failure can result from any disorder that affects the heart's ability to contract and/or relax.
• Coronary artery disease is the most common cause of systolic heart failure, accounting for nearly 70% of cases.
• Diastolic dysfunction is a common cause of heart failure, especially in the elderly, females, obese individuals, and those with hypertension, atrial fibrillation, and diabetes.

Compensatory Mechanisms in Heart Failure

• The heart's decrease in pumping capacity results in compensatory responses to maintain cardiac output.
• Compensatory responses include tachycardia and increased contractility, fluid retention and increased preload, vasoconstriction and increased afterload, and ventricular hypertrophy and remodeling.