Management of Heart Failure Patient with CKD

Abstract

CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m² Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m²). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.

Keywords: chronic kidney disease; dialysis; heart failure.

Figure 1.

The figure shows level of evidencefor heart failure management in patients with CKD with different levels of kidney function. Adapted from the Kidney Disease Improving Global Outcomes Consensus Conference report (1). The increasing levels of evidence for improved outcomes (mortality and hospitalizations) are shown for each therapy on the y axis, with increasing levels of GFR on the x axis. Evidence is strong for BBs, ACEis, ARBs, and MRAs and moderate for CRTs and ivabradine for eGFR>30 ml/min per 1.73 m². ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β-blocker; CKD G3a–3b, chronic kidney disease grade 3a and 3b; CKD G4, chronic kidney disease grade 4; CKD G5D, chronic kidney disease GFR category 5 patient on dialysis; CKD G5 ND, chronic kidney disease GFR category 5 patient not on dialysis; CRT, cardiac resynchronization therapy; EF, ejection fraction; H-ISDN, hydralazine-isosorbide dinitrate; ICD, implantable cardioverter defibrillator; IV, intravenous; LBBB, left bundle branch block; MRA, mineralocorticoid receptor antagonist; PO, oral; QRS, QRS wave length in electrocardiogram.

Figure 2.

The figure shows management strategy for patients with heart failure and CKD, including KRT. Adapted from the Kidney Disease Improving Global Outcomes Consensus Conference report (1). Stepwise, evidence-based drug therapy (increasing levels of evidence from the top to bottom of the pyramid) is shown in the middle. The bars on either side of the pyramid show relevant supportive treatment. AF, atrial fibrillation; ARNI, angiotensin receptor neprilysin inhibitor; CKD-MBD, CKD with mineral and bone disorder; CRRT, continuous KRT; i.v., intravenous; NSAID, nonsteroidal anti-inflammatory drug; RAASi, renin-angiotensin-aldosterone system inhibitor.