Guidelines-Based Treatment of HFrEF with Normal Coronaries (Non-Ischaemic Cardiomyopathy)

Establishing the Diagnosis First

• Inflammatory/myocarditis → immunosuppression may be considered
• Alcohol-related → abstinence is mandatory
• Tachycardia-mediated → rate/rhythm control is primary
• Sarcoid/amyloid/haemochromatosis/peripartum → specific therapies exist
• Idiopathic dilated cardiomyopathy (DCM) → standard GDMT applies

The Four Pillars of GDMT — The Foundation of Treatment

Class I, Level A recommendation for all four pillars in symptomatic HFrEF (LVEF ≤40%).

Pillar 1 — ARNI (Preferred) or ACEi/ARB

• Sacubitril/valsartan (ARNI) is preferred over ACEi for all stable, tolerant HFrEF patients — start at 24/26 mg BD if ACEi-naive or if switching from ACEi (wash-out 36 hours to avoid angioedema).
• ACEi (enalapril, lisinopril, ramipril) — use if ARNI is not tolerated or unavailable. Class I, Level A.
• ARB (candesartan, valsartan) — use if ACEi intolerant (cough). Class I, Level A.
• Not to combine ACEi + ARB; do not combine ACEi/ARB with ARNI.

Pillar 2 — Evidence-Based Beta-Blockers

• Initiate only when patient is euvolaemic and haemodynamically stable.
• Do not start or up-titrate during acute decompensation.
• Titrate over weeks to maximum tolerated dose (e.g., carvedilol target 25 mg BD; bisoprolol target 10 mg OD).

Pillar 3 — Mineralocorticoid Receptor Antagonist (MRA)

• Indicated for LVEF ≤35% and NYHA class II–IV (with adequate renal function and normokalemia).
• Check K⁺ and eGFR before starting; recheck at 1–2 weeks.
• Avoid if eGFR <30 mL/min/1.73m² or K⁺ >5.0 mmol/L.
• Spironolactone is equally effective to eplerenone but has more anti-androgenic side effects.

Pillar 4 — SGLT2 Inhibitor

• Dapagliflozin or empagliflozin 10 mg OD — benefit is independent of diabetes status.
• Can be initiated at any time, including during hospitalisation, regardless of haemodynamics.
• SGLT2i and MRA together have additive hyperkalaemia protection (SGLT2i modestly lowers K⁺).
• Also improves eGFR trajectory — mild GFR dip on initiation is expected; do not stop.

Additional Pharmacotherapy

Ivabradine (Class IIa)

• Indicated if sinus rhythm, resting HR ≥70 bpm despite maximum tolerated beta-blocker (or if beta-blocker not tolerated), NYHA II–III, LVEF ≤35%.
• Reduces HF hospitalisation (SHIFT trial — 18% ↓ composite of CV death + HF hospitalisation).
• Not for AF patients — no benefit.

Hydralazine + Isosorbide Dinitrate (H-ISDN) (Class I for Black patients; Class IIa for others)

• Class I for self-identified African American patients with NYHA III–IV despite ACEi/BB/MRA (A-HeFT trial — trial stopped early, 43% ↓ mortality).
• Class IIa for patients who cannot tolerate ACEi/ARB/ARNI due to renal failure or hyperkalaemia.

Vericiguat (Class IIb)

• Soluble guanylate cyclase stimulator. For high-risk patients with recent worsening HF event (hospitalisation or IV diuretics).
• Modestly reduces CV death/HF hospitalisation (VICTORIA trial — 10% relative reduction).

Digoxin (Class IIb)

• May be considered for symptom control and reducing HF hospitalisation in patients already on GDMT who have persistent symptoms.
• No mortality benefit (DIG trial). Use at low doses; target serum level 0.5–0.9 ng/mL.
• Particularly useful if co-existing AF requiring rate control.

Diuretics (Class I for congestion)

• Loop diuretics (furosemide, torsemide) are the cornerstone of decongestion — not proven to reduce mortality but essential for symptom control and quality of life.
• Torsemide has superior bioavailability vs furosemide; TRANSFORM-HF trial showed similar outcomes but many favour torsemide for consistency.
• Use minimum effective dose; titrate to achieve euvolaemia.

Device Therapy

ICD — Primary Prevention of SCD

Key point for non-ischaemic CMP: Wait ≥3 months of optimal GDMT before reassessing LVEF — significant recovery (reverse remodelling) is common, and many will no longer meet ICD criteria.

CRT / CRT-D

• CRT improves LVEF, NYHA class, 6-minute walk, reduces HF admissions, and reduces mortality (RR 0.79, 95% CI 0.66–0.96).
• In NICM with wide QRS + low LVEF: consider CRT-D (combined resynchronisation + defibrillator).

Cardiac Contractility Modulation (CCM)

• For NYHA II–III, LVEF 25–45%, QRS <130 ms (not eligible for CRT) — Class IIb.

Advanced Heart Failure — When GDMT Fails

• Refer to advanced HF centre — Class I recommendation.
• Consider LVAD (left ventricular assist device) as bridge-to-transplant or destination therapy.
• Heart transplantation remains the gold standard for end-stage HFrEF in eligible candidates.
• Inotropic support (dobutamine, milrinone) as bridge to decision in cardiogenic shock.

Comorbidity Management (Integral to HF Care)

Monitoring Framework

• BNP/NT-proBNP — titrate therapy to achieve lowest achievable level; serial reduction correlates with outcomes.
• Repeat echo at 3–6 months after initiating GDMT — significant LVEF recovery common in NICM.
• Renal function and electrolytes — check 1–2 weeks after starting/up-titrating RAAS agents, MRA, SGLT2i.
• Multidisciplinary HF team (cardiologist, HF nurse, pharmacist) — reduces rehospitalisation.

Summary: Rapid Initiation Algorithm

Day 1–7:     Start SGLT2i + low-dose ARNI (or ACEi if ARNI unavailable)
Week 1–2:    Add MRA once K⁺ confirmed safe
Week 2–4:    Add beta-blocker once euvolaemic
Month 1–3:   Up-titrate all four to maximum tolerated doses
Month 3:     Reassess LVEF — if still ≤35% + NYHA II–III → assess for ICD/CRT

Contrast-Associated AKI (CA-AKI): Current Guidelines

Terminology — Getting the Definition Right

• Serum creatinine rise ≥0.3 mg/dL (≥26.5 µmol/L), OR
• Serum creatinine ≥1.5× baseline, OR
• Urine output <0.5 mL/kg/h for ≥6 hours

Important nuance: Recent propensity-matched studies have challenged the magnitude of CIN risk, particularly with intravenous contrast in CT. The risk is significantly higher with intra-arterial contrast (cardiac angiography) than intravenous contrast — these populations should not be extrapolated to each other.

Step 1 — Risk Assessment (KDIGO 2026, Practice Points 4.8.1–4.8.2)

High-risk patient features:

• CKD — eGFR <45 mL/min/1.73 m² (ESUR/CAR threshold); risk increases markedly at eGFR <30
• Diabetes mellitus
• Age >60 years
• Acute heart failure / haemodynamic instability / cardiogenic shock
• Volume depletion (most significant modifiable risk factor)
• Concurrent nephrotoxin use (NSAIDs, aminoglycosides, calcineurin inhibitors)
• Large contrast volume
• Prior AKI
• Peripheral artery disease (independent risk factor for post-angiography AKI)

Risk scoring (for intra-arterial contrast — cardiac procedures):

KDIGO Practice Point 4.9.1.1:

Weigh risks vs benefits. If benefit exceeds risk, do not defer or delay the procedure. Consider alternative imaging (ultrasound, non-contrast MRI, CO₂ angiography) when equally diagnostic.

Step 2 — Choice of Contrast Agent

• Iso-osmolar: iodixanol (Visipaque) — particularly preferred in CKD + intra-arterial use
• Low-osmolar: iohexol, iopamidol, iopromide — acceptable
• High-osmolar agents (ionic): avoid in all high-risk patients

Step 3 — Prevention: Fluid Administration

The cornerstone of prevention remains intravenous volume expansion.

IV Hydration Protocol:

• Isotonic saline (0.9% NaCl) — first-line agent
  • Standard regimen: 1–1.5 mL/kg/h for 6–12 hours before AND 6–12 hours after procedure
  • Rapid pre-procedure regimen: 3 mL/kg/h for 1 hour before, then 1 mL/kg/h for 6 hours after
• Sodium bicarbonate (1.26% or 1.4%) — no longer preferred; PRESERVE trial (2018) definitively showed no benefit over saline; not recommended by ACR 2018 or KDIGO 2026
• Hold diuretics during hydration if patient is not volume overloaded (KDIGO 2026 Practice Point 4.9.2.2)

Oral vs IV hydration:

• IV preferred when practical (ensures certainty of volume)
• Oral hydration (water/saline) may be an acceptable alternative in low-risk outpatients with mild CKD, but is not supported by strong evidence for high-risk patients

RenalGuard system (diuresis-matched hydration):

• Furosemide-induced forced diuresis matched to urine output with simultaneous IV fluid replacement
• Some RCT evidence of benefit in CKD/high-risk PCI patients (meta-analysis PMID 36801376) — Class IIb option for high-risk interventional procedures

Step 4 — Drugs That Do NOT Work (Do Not Use)

Step 5 — Drug Management Around Contrast Procedures

Metformin

• In patients with eGFR >30 and no AKI: no need to routinely stop metformin before IV contrast (KDIGO 2024 CKD guideline — this is a significant change from older advice)
• In patients with eGFR <30 or active AKI: withhold metformin, hold 48h post-procedure, reassess renal function before restarting
• Risk is lactic acidosis if AKI develops (not direct nephrotoxicity)

RAS Inhibitors (ACEi/ARBs)

• KDIGO 2026 Recommendation 4.9.3.1 (2C): Suggests not routinely withholding RASi before contrast procedures
• Clinical caveat: in haemodynamically unstable patients or emergency procedures, use individual judgement — evidence from SPACE trial (2024) confirms harm from routine perioperative RASi withholding

SGLT2 Inhibitors

• Hold 24–48h before elective procedures requiring contrast, especially if prolonged fasting planned (risk of euglycaemic DKA)
• KDIGO CKD 2024: Withhold during prolonged fasting, surgery, or critical illness

NSAIDs

• Stop before procedure — these are independent nephrotoxins that compound contrast risk, especially in volume-depleted patients

Step 6 — High-Dose Statins (for Cardiac Procedures)

• ACC/AHA 2022 Coronary Revascularization Guideline: Recommends high-dose statins (e.g., atorvastatin 80 mg) before PCI in statin-naive patients with CKD — pleiotropic anti-inflammatory effects reduce CA-AKI risk
• Multiple RCTs support pre-procedural statin loading in high-risk CKD patients undergoing coronary angiography/PCI

Step 7 — Procedural Technique (Cardiac Interventions)

• Radial access preferred over femoral access — associated with lower CA-AKI risk (ACC/AHA)
• Minimise contrast volume — use biplane views, review imaging before contrast injection, use contrast-saving technology (IVUS, FFR)
• Avoid high-osmolar contrast and repeat contrast within 48–72h
• Contrast volume/creatinine clearance ratio should ideally be <3.7

Step 8 — Monitoring Post-Procedure

• Check serum creatinine (and urine output) at 24–48 hours post-procedure in high-risk patients
• In most patients, CA-AKI is transient — creatinine peaks at 96h, returns to baseline in 7–10 days
• If creatinine does not return to baseline within 2–3 weeks, investigate for underlying CKD progression or atheroembolic disease (in arterial procedures)
• Consider nephrology referral for AKI requiring dialysis or persistent AKI at 3 months

Summary Table: CA-AKI Prevention — What Works, What Doesn't