Stage C Heart Failure: Definition and Management
Stage C heart failure represents patients with structural heart disease who have current or prior symptoms of heart failure, requiring comprehensive guideline-directed medical therapy (GDMT) including ACE inhibitors/ARBs, beta-blockers, diuretics, and consideration for device therapy to reduce mortality and hospitalizations. 1
Definition and Clinical Characteristics
Stage C encompasses patients with structural heart disease who are currently symptomatic or have a history of heart failure symptoms 1. This stage corresponds to NYHA functional classes I through IV, ranging from no limitation of physical activity to symptoms at rest 1. The key distinction from Stage B is the presence of symptoms—either current or historical—in patients with underlying structural abnormalities 2.
Core Pharmacologic Management
Foundation Therapy for Reduced Ejection Fraction (HFrEF)
ACE inhibitors or ARBs must be initiated in all Stage C patients with reduced ejection fraction to prevent disease progression and reduce mortality 2. For patients intolerant to ACE inhibitors, ARBs serve as the alternative 2. The 2024 ESC guidelines further recommend sacubitril/valsartan as a replacement for ACE inhibitors or ARBs in HFrEF patients to reduce heart failure hospitalizations and death 1.
Beta-blockers should be used in all Stage C patients with reduced ejection fraction 2. These agents prevent symptomatic worsening and improve survival when combined with ACE inhibition 2.
Diuretics are essential for patients with evidence or history of fluid retention 1, 2. They provide symptomatic relief from volume overload and reduce congestive symptoms 1. Monitor closely for electrolyte abnormalities and dehydration during diuretic therapy 2.
Aldosterone receptor antagonists should be added for patients with NYHA class II through IV heart failure who have an ejection fraction of 35% or less 2. Close monitoring for hyperkalemia and renal insufficiency is mandatory 2.
SGLT2 inhibitors (dapagliflozin or empagliflozin) are now recommended as foundational therapy for HFrEF to reduce heart failure hospitalizations and death 1. These agents also benefit patients with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) 1.
Management of Heart Failure with Preserved Ejection Fraction (HFpEF)
Blood pressure control is the primary intervention for HFpEF, following published clinical practice guidelines 1. Beta-blockers, ACE inhibitors, and ARBs are reasonable for hypertension management in this population 1.
Diuretics should be used for symptomatic relief from volume overload 1.
SGLT2 inhibitors (dapagliflozin or empagliflozin) are recommended to reduce heart failure hospitalizations and cardiovascular death in HFpEF 1.
Device Therapy Considerations
Implantable Cardioverter-Defibrillator (ICD)
ICD therapy is recommended for primary prevention of sudden cardiac death in selected HFrEF patients at least 40 days post-MI with LVEF ≤35% and NYHA class II or III symptoms on chronic GDMT, who are expected to live >1 year 1.
ICD therapy is also recommended for patients at least 40 days post-MI with LVEF ≤30% and NYHA class I symptoms while receiving GDMT 1.
An important caveat: ICD benefit is uncertain in patients with high risk of non-sudden death, such as those with frequent hospitalizations, frailty, or severe comorbidities 1.
Cardiac Resynchronization Therapy (CRT)
CRT is indicated for patients with LVEF ≤35%, sinus rhythm, and LBBB with QRS ≥150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT 1. This represents the strongest indication with Class I, Level A evidence 1.
CRT can be useful for patients with LVEF ≤35%, sinus rhythm, LBBB with QRS 120-149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT 1.
CRT can be useful in atrial fibrillation patients with LVEF ≤35% on GDMT if they require ventricular pacing or otherwise meet CRT criteria, and AV nodal ablation or rate control allows near 100% ventricular pacing 1.
Lifestyle Modifications
Exercise training or regular physical activity is recommended as safe and effective for Stage C patients who are able to participate, to improve functional status 1. This carries Class I, Level A evidence 1.
Sodium restriction is reasonable for symptomatic heart failure patients to reduce congestive symptoms 1. However, there are no specific recommendations for caloric intake or dietary composition beyond this 1.
The DASH diet and Mediterranean diet patterns have shown benefits in preventing heart failure progression, though specific data in established Stage C heart failure is limited 1.
Critical Implementation Strategies
Medication Titration Protocol
When initiating or adjusting GDMT, follow this systematic approach 1:
- Review and adjust diuretic and vasodilator doses before starting ACE inhibitors
- Avoid excessive diuresis before treatment initiation
- Monitor blood urea nitrogen, creatinine, potassium, and sodium with each medication adjustment affecting the renin-angiotensin-aldosterone system
- Monitor blood pressure and heart rate with each dose adjustment
- Assess symptoms and functional capacity regularly
- Reassure patients that fatigue and weakness with dosage increases are often transient and resolve within days
- Discourage sudden discontinuation of GDMT medications without discussion
- Consider temporary adjustments during acute noncardiac illnesses (respiratory infections, dehydration risk)
- Educate patients about expected benefits including myocardial reverse remodeling, increased survival, and improved functional status
Enrollment in Multidisciplinary Programs
Stage C patients should be enrolled in a multidisciplinary heart failure management program to reduce heart failure hospitalizations and improve survival 1. This represents a Class I, Level A recommendation 1.
Common Pitfalls to Avoid
Do not use thiazolidinediones in patients with LVEF <50%, as they increase heart failure risk and hospitalizations 3.
Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) with negative inotropic effects in patients with LVEF <50%, as they may be harmful 3.
Nutritional supplementation is not recommended in HFpEF 1.
Patients with advanced heart failure may be less tolerant of neurohormonal antagonism (ACE inhibitors, beta-blockers) than those with mild symptoms, as these mechanisms support circulatory homeostasis in advanced disease 2. However, this does not negate the mortality benefit—careful titration is key.
Monitoring Requirements
For hospitalized Stage C patients after stabilization 2:
- Monitor heart rate, rhythm, blood pressure, and oxygen saturation continuously for at least 24 hours
- Assess heart failure symptoms daily
- Measure fluid intake/output, weight, jugular venous pressure, and extent of edema daily
- Monitor blood urea nitrogen, creatinine, potassium, and sodium daily during IV therapy and when adjusting RAAS medications
Before discharge, ensure 2:
- The acute episode has resolved
- Congestion is absent
- A stable oral diuretic regimen has been established for at least 48 hours
- Long-term disease-modifying therapy has been optimized