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Cardiolucent

Treatment

Heart Failure Management (ARNIs, SGLT2 inhibitors)

Quadruple therapy and beyond — the modern medical regimen for heart failure.

Heart failure management has been transformed over the past decade by two newer drug classes: angiotensin receptor-neprilysin inhibitors (ARNIs, brand name Entresto) and sodium-glucose co-transporter-2 (SGLT2) inhibitors (empagliflozin, dapagliflozin). Together with beta-blockers and mineralocorticoid receptor antagonists (MRAs), they form the "four pillars" of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), and SGLT2 inhibitors are now also standard for heart failure with preserved ejection fraction (HFpEF). The goal is to lower hospitalization rates, slow disease progression, and extend life — but only if doses are optimized over time. Dr. Kedan builds and titrates the full regimen rather than starting one drug and stopping.

What This Treatment Approach Includes

  • Assessment of ejection fraction, symptoms, volume status, and biomarkers (BNP/NT-proBNP)
  • Initiation and uptitration of the four pillars: ARNI, beta-blocker, MRA, SGLT2 inhibitor
  • Diuretic management for fluid overload — balancing congestion against kidney function
  • Iron deficiency screening and IV iron when appropriate
  • Coordination of advanced therapies (ICD, CRT, transplant evaluation) through Cedars-Sinai
  • POCUS at office visits to assess volume status and ventricular function
  • Direct access for symptom changes — weight gain, breathlessness, or fatigue

How It Works

ARNIs combine an angiotensin II receptor blocker with neprilysin inhibition, simultaneously blocking harmful neurohormonal activation and enhancing protective natriuretic peptides. SGLT2 inhibitors, originally diabetes medications, reduce heart failure hospitalizations and cardiovascular death through mechanisms that include diuresis, improved myocardial energetics, and reduced cardiac stress — independent of glucose lowering. Beta-blockers and MRAs round out the regimen by blocking adrenergic and aldosterone-mediated injury to the heart.

Who This Is For

  • Heart failure with reduced ejection fraction (HFrEF, EF ≤ 40%)
  • Heart failure with mildly reduced ejection fraction (HFmrEF, EF 41–49%)
  • Heart failure with preserved ejection fraction (HFpEF, EF ≥ 50%) — SGLT2 inhibitors
  • Recent heart failure hospitalization, where rapid titration matters most
  • Patients already on partial therapy whose regimen has stalled below target doses
  • Diabetic cardiomyopathy or coexisting type 2 diabetes
  • Symptomatic patients on stable therapy who may benefit from device evaluation

Monitoring and Follow-Up

Initiation and uptitration require close monitoring of kidney function, potassium, blood pressure, and symptoms — typically every two to four weeks during titration, then less frequently once a stable dose is reached. Daily weights are a core self-monitoring tool, and a rise of two to three pounds over a few days usually warrants a call. The concierge model lets Dr. Kedan adjust diuretics or address rising potassium the same day rather than after a hospitalization happens.

How Cardiolucent Manages This

Many heart failure patients are on partial therapy at submaximal doses because uptitration is logistically demanding. Dr. Kedan structures the practice to make full guideline-directed therapy achievable — extended visits for shared decision-making, same-day labs, coordinated cardiology and primary care communication, and direct phone access during titration. When advanced therapies are warranted (ICD, cardiac resynchronization therapy, transplant evaluation), care is coordinated through Cedars-Sinai with Dr. Kedan staying involved as the longitudinal cardiologist.

Common Questions

Frequently Asked Questions

What are the 'four pillars' of heart failure therapy?
The four pillars are the four drug classes proven to reduce death and hospitalization in heart failure with reduced ejection fraction: an ARNI (or ACE inhibitor / ARB if ARNI is not appropriate), a beta-blocker, a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and an SGLT2 inhibitor. Used together at target doses, they produce a survival benefit that exceeds any single therapy.
What is an ARNI and how is it different from an ACE inhibitor or ARB?
An ARNI combines an angiotensin receptor blocker (valsartan) with a neprilysin inhibitor (sacubitril). It both blocks harmful neurohormonal signaling and enhances the body's protective natriuretic peptides — something ACE inhibitors and ARBs do not do. For most HFrEF patients, an ARNI outperformed an ACE inhibitor in head-to-head trials and is the preferred first choice when tolerated.
Why are SGLT2 inhibitors used in heart failure even without diabetes?
SGLT2 inhibitors were originally developed for type 2 diabetes, but large heart failure trials showed they reduce cardiovascular death and hospitalization in patients with HFrEF and HFpEF — whether or not they have diabetes. The benefit appears to be independent of glucose lowering and is mediated by effects on diuresis, myocardial energetics, and inflammation.
Who is a candidate for this regimen?
Almost every patient with heart failure and a reduced ejection fraction is a candidate for some version of the four-pillar regimen, with the specific agents chosen based on kidney function, blood pressure, potassium, and other medications. Patients with preserved ejection fraction are candidates for SGLT2 inhibitor therapy. The conversation is about which specific agents and doses, not whether to treat.
What side effects are common?
Side effects vary by class: ARNIs and other renin-angiotensin agents can lower blood pressure and raise potassium; beta-blockers can cause fatigue and slow heart rate; MRAs can raise potassium and rarely cause breast tenderness; SGLT2 inhibitors can cause genital yeast infections, dehydration, and rarely euglycemic ketoacidosis. Most side effects are manageable with dose adjustments and timing changes.
How long will the titration take?
Typical titration to target doses takes three to six months, with dose increases every two to four weeks if kidney function, potassium, and blood pressure tolerate. Some patients reach target doses quickly; others require slower titration or end at submaximal but tolerated doses. The goal is the maximum tolerated dose of each pillar — not necessarily the highest possible dose.
Will I be on these medications for life?
In most cases, yes. The regimen treats the underlying neurohormonal activation that drives heart failure progression — stopping the medications generally allows that progression to resume. In a subset of patients whose ejection fraction recovers fully on therapy, the question of carefully reducing therapy may arise, but it is approached cautiously and based on imaging and symptom data.
What lifestyle changes are essential?
Daily weights, sodium awareness (typically under 2 to 3 grams daily), modest fluid attention for some patients, regular aerobic activity within safe limits, and tobacco cessation are foundational. Alcohol moderation matters, especially with alcohol-related cardiomyopathy. Cardiac rehabilitation is recommended for most patients after hospitalization or new diagnosis.
When are devices (ICD, CRT, LVAD) considered?
An implantable cardioverter-defibrillator (ICD) is considered when ejection fraction remains 35% or below after at least three months of optimized therapy. Cardiac resynchronization therapy (CRT) is considered with left bundle branch block and persistently reduced ejection fraction. Advanced therapies — LVAD or transplant — are considered for end-stage disease. Dr. Kedan coordinates these evaluations through Cedars-Sinai.
How do I start managed heart failure care with Dr. Kedan?
Schedule a consultation at the Beverly Hills office with prior records, recent echocardiogram, and a current medication list. Cardiolucent is a concierge practice and does not bill Medicare or insurance, though a detailed superbill is provided for out-of-network reimbursement. Call (310) 304-5555 or use the contact form.

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Medical Disclaimer

The information on this site is for general educational purposes only and is not medical advice, diagnosis, or treatment. Reading this site does not create a doctor–patient relationship. Always consult a qualified healthcare professional for personal guidance. If this is an emergency, call 911. Mentions of medications, devices, or procedures are informational and not endorsements. Full medical disclaimer.

†Some listed indications involve investigational/off-label use. Learn more.