Sequencing Quadruple Therapy in HFrEF with CKD and Hyperkalaemia
A 71-year-old woman with ischaemic cardiomyopathy (LVEF 27% on echocardiography 4 months ago) is admitted with NYHA class III dyspnoea. She has permanent atrial fibrillation with a resting ventricular rate of 78/min, type 2 diabetes, hypertension and stable stage 3b chronic kidney disease (eGFR 34 mL/min/1.73 m²). Her medications are furosemide 40 mg daily, carvedilol 3.125 mg twice daily and sacubitril/valsartan 24/26 mg twice daily. Blood pressure is 118/70 mmHg; the pulse is 78/min and irregular; weight has increased 3 kg in two weeks. There are bibasilar crackles and the JVP is 10 cm. Laboratory results: potassium 5.1 mmol/L, sodium 136 mmol/L, creatinine 2.0 mg/dL, haemoglobin 11.2 g/dL, ferritin 180 ng/mL and transferrin saturation 15%. She has never received a mineralocorticoid receptor antagonist or an SGLT2 inhibitor. The ECG shows atrial fibrillation with a QRS duration of 148 ms and left bundle branch block morphology, and she has no device. She asks whether another tablet is worth the risk and whether she needs a device.
1. Set out the order in which you will add disease-modifying therapy, with doses and the specific reasoning about potassium and renal function.
Read the worked answer
Start the SGLT2 inhibitor today and prepare for the MRA over the next week.
SGLT2 inhibitor first. Dapagliflozin 10 mg or empagliflozin 10 mg once daily is recommended down to an eGFR of about 20 mL/min/1.73 m² and does not raise potassium, so the current potassium of 5.1 mmol/L is not a barrier. Expect a small reversible creatinine rise of up to 30% in the first weeks; do not stop the drug for this. If she becomes euvolemic, reduce furosemide rather than withdrawing the SGLT2 inhibitor. Counsel on genital hygiene and sick-day rules (hold during acute illness with poor intake).
MRA second, after lowering potassium. Spironolactone reduces mortality by roughly 30% in HFrEF, but most protocols require K <5.0 mmol/L and eGFR >30. At 5.1 mmol/L the drug is not started today. Instead:
- Stop NSAIDs, potassium supplements and potassium-containing salt substitutes.
- Dietitian review of potassium intake.
- Consider patiromer 8.4 g daily if diet alone is insufficient.
- Recheck potassium and creatinine in 3–7 days. When K is below 5.0, start spironolactone 12.5 mg daily and recheck potassium and creatinine at 1 week and 4 weeks. Eplerenone 25 mg is an alternative with fewer antiandrogenic effects.
Then optimise. Uptitrate sacubitril/valsartan and carvedilol as BP and potassium allow, and continue anticoagulation for atrial fibrillation. Frame this as sequencing, not as denying her therapy.
2. Does she need a CRT or ICD now? Give the indication, the timing, and how permanent atrial fibrillation alters your decision.
Read the worked answer
She is a resynchronization candidate, but not during this admission.
Why CRT. She has HFrEF (LVEF 27%), NYHA III symptoms and left bundle branch block with a QRS of 148 ms - the morphology with the greatest likelihood of benefit, although the strongest evidence is for QRS ≥150 ms, so her ECG should be repeated and the exact duration confirmed. Criteria are LVEF ≤35%, NYHA II–IV, LBBB with broad QRS, on optimal medical therapy. CRT improves symptoms and survival and reduces sudden death, so a CRT-D is preferable to CRT-P when life expectancy exceeds 1 year.
Timing. She is decompensated (3 kg gain), so the EF and functional class must be reassessed after at least 3 months of optimized quadruple therapy, including the SGLT2 inhibitor and MRA. If LVEF remains ≤35%, proceed with CRT-D.
Atrial fibrillation. With permanent AF, biventricular pacing must be near-complete (>95%) for benefit. If the ventricular rate cannot be controlled or pacing is inadequate, AV node ablation is appropriate and does not worsen outcomes once pacing is secure. Her ventricular rate of 78/min is acceptable now, but ambulatory rate monitoring is needed before implantation. Involve electrophysiology early and document QRS morphology on a 12-lead ECG.
3. How will you manage her iron studies and residual congestion, and what monitoring plan will you put in place after discharge?
Read the worked answer
Iron deficiency is present and treatable. Ferritin 180 ng/mL with transferrin saturation 15% meets the HFrEF definition of iron deficiency (ferritin <100 ng/mL, or 100–299 ng/mL with TSAT <20%). Give intravenous ferric carboxymaltose (typically 500–1000 mg depending on weight and haemoglobin), which improves symptoms, exercise capacity and quality of life and reduces heart failure hospitalisation. Oral iron is poorly absorbed in this setting and is not a substitute. Recheck haemoglobin and iron studies at 3 months.
Residual congestion. The 3 kg weight gain, crackles and JVP of 10 cm mean she is above dry weight. Increase furosemide temporarily, for example to 80 mg daily or with a short course of metolazone 2.5 mg, guided by daily weights, and reduce once euvolemic. Avoid over-diuresis, which worsens renal function and blocks RAAS inhibitor and MRA use.
Monitoring plan.
- Basic metabolic panel 1 week after each medication change, then at 1 and 3 months.
- Home weight and BP diary; a weight gain of more than 2 kg in 3 days should trigger contact.
- Repeat echocardiography at 3 months for device decision.
- Anticoagulation review with CHA2DS2-VASc and renal dosing.
- If an MRA cannot be tolerated despite potassium binders, document it and consider hydralazine/isosorbide dinitrate; ivabradine does not apply because she is not in sinus rhythm.