What is the pathophysiology and treatment of heart failure?

Pathophysiology and Treatment of Heart Failure

Heart failure is a complex syndrome characterized by the heart's inability to maintain sufficient cardiac output to meet metabolic requirements, resulting from multiple interrelated abnormalities including LVOT obstruction, diastolic dysfunction, mitral regurgitation, myocardial ischemia, and arrhythmias. 1

Pathophysiology

Vicious Cycle of Heart Failure

• Heart failure begins with a critical inability of the myocardium to maintain adequate cardiac output to meet peripheral circulation demands, triggering a vicious cycle that leads to progressive deterioration 1
• After cardiac injury, structural, neurohumoral, cellular, and molecular mechanisms are activated as a network to maintain physiological functioning 2

Neurohormonal Activation

• Two key neurohumoral systems activated in heart failure are the renin-angiotensin-aldosterone system and sympathetic nervous system 1
• Early in heart failure, drops in cardiac output lead to decreased organ perfusion, triggering compensatory increases in adrenergic drive and release of neurohormones like norepinephrine 1
• Initially compensatory, chronic activation of these systems becomes maladaptive, causing progressive myocardial deterioration and portending poor prognosis 1

Ventricular Remodeling

• Heart failure results in ventricular remodeling with increased ventricular volume and wall thickness 3
• Prolonged mechanical stress, cardiac fibrosis, and necrosis promoted by norepinephrine contribute to remodeling, resulting in a dilated, less contractile cardiac chamber 1
• Norepinephrine down-regulates β1-adrenergic receptors and uncouples β2-adrenergic receptors, further decreasing contractile function 1

Congestion and Fluid Overload

• Systemic venous congestion decreases venous return to right cavities (causing systemic interstitial fluid accumulation) and increases left filling pressures (causing pulmonary fluid accumulation) 1
• Congestion leads to impaired organ perfusion, particularly affecting kidneys, liver, lungs, and gut 1
• Hemodynamic congestion precedes clinical congestion by days or weeks, with clinical symptoms appearing when compensatory mechanisms are overwhelmed 4

Treatment Approaches

Pharmacological Therapy

Diuretics

• Diuretics are essential for relieving congestion and achieving euvolemia in heart failure patients 1
• Treatment with diuretics should be titrated to resolve clinical evidence of congestion to reduce symptoms and rehospitalizations 1
• Fluid restriction of 1.5-2 L/day may be considered in patients with severe symptoms of heart failure, especially with hyponatremia 1

Neurohormonal Blockade

• ACE inhibitors like lisinopril reduce signs and symptoms of heart failure including edema, rales, paroxysmal nocturnal dyspnea, and jugular venous distention 5
• In clinical trials, lisinopril combined with digitalis and diuretics reduced orthopnea, presence of third heart sound, and improved NYHA classification 5
• The ATLAS trial showed that higher doses of lisinopril (35 mg) had outcomes at least as favorable as lower doses (2.5 mg) in patients with systolic heart failure 5
• β-blockers, initially contraindicated in heart failure, are now recognized as beneficial by reversing the deleterious effects of chronic adrenergic stimulation 1

Other Medications

• Angiotensin receptor neprilysin inhibitors, vasodilator peptides, and drugs that enhance Ca++ uptake by the sarcoplasmic reticulum are promising new therapies 6
• Digoxin may be used for symptom management alongside diuretics and vasodilators 7

Surgical and Device Therapies

• For patients with ischemic heart disease, coronary artery revascularization via CABG or percutaneous intervention is indicated for those with angina and suitable coronary anatomy 1
• CABG to improve survival is reasonable in patients with mild to moderate LV systolic dysfunction and significant multivessel CAD when viable myocardium is present 1
• Ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation are options for advanced heart failure 3
• Heart transplantation may be considered for systolic or intractable diastolic dysfunction associated with severe unrelenting symptoms 1

Monitoring and Follow-up

• Regular weight monitoring is recommended, with patients advised to alert healthcare providers if sudden unexpected weight gain of >2 kg in 3 days occurs 1
• Natriuretic peptides, particularly NT-proBNP, are useful for assessing volume status and guiding decongestive therapies 1
• A decrease greater than 30% in natriuretic peptides by day 5 after fluid removal with a discharge value <1500 pg/mL indicates good prognosis 1

Clinical Course and Prognosis

• Heart failure can progress through three relatively discrete but not mutually exclusive pathways: sudden cardiac death due to ventricular arrhythmias, progressive heart failure with exertional dyspnea, and atrial fibrillation associated with heart failure and thromboembolism risk 1
• Congestive heart failure carries a 50% 5-year mortality despite advances in treatment 3
• Clinical congestion is associated with a 2-3 times increase in 60-day mortality, and patients with ≥3 residual signs of congestion have only 41% 2-year survival rates 4

Common Pitfalls and Caveats

• Symptoms may be difficult to interpret, particularly in elderly patients, obese individuals, and women 1
• There is a poor relationship between symptoms and the severity of cardiac dysfunction, though symptoms may relate to prognosis particularly if persisting after therapy 1
• Worsening renal function is common with heart failure treatment; in studies with lisinopril, reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of heart failure patients on concomitant diuretic therapy 5
• Hyperkalemia occurred in 4.8% of lisinopril-treated patients with heart failure and requires monitoring 5