INTRODUCTION — Patients with end-stage kidney disease requiring dialysis are at increased risk for development of heart failure (HF). Factors that may contribute to HF in the dialysis patient include fluid overload, poorly-controlled hypertension increasing afterload, left ventricular (LV) diastolic dysfunction (often associated with LV hypertrophy), arterial stiffness, LV systolic dysfunction, uremic toxin accumulation, anemia, and valvular heart disease. A high-output state caused by shunting through hemodialysis arteriovenous access can also precipitate HF, particularly in patients with underlying ventricular dysfunction. Ventricular dysfunction and cardiovascular drugs can also reduce hemodynamic reserve, making the patient more vulnerable to episodes of hypotension during dialysis. (See "Overview of screening and diagnosis of heart disease in patients on dialysis", section on 'Causes and risk factors' and "Evaluation and management of heart failure caused by hemodialysis arteriovenous access" and "Clinical manifestations, diagnosis, and management of high-output heart failure".)
This topic will discuss the specific measures in the management and prevention of HF in dialysis patients.
●General measures for all dialysis patients to prevent or treat HF are discussed separately. (See "Overview of the management and prevention of heart failure in dialysis patients".)
●Screening for heart disease and diagnosis of HF in dialysis patients are discussed separately. (See "Overview of screening and diagnosis of heart disease in patients on dialysis".)
●The general management of chronic kidney disease in adults is discussed separately. (See "Overview of the management of chronic kidney disease in adults".)
APPROACH TO MANAGEMENT — The approach to management or prevention of HF in the dialysis patient varies depending upon the clinical presentation.
●For all dialysis patients, general measures to manage or prevent HF apply, including adequate volume control with loop diuretic therapy (if there is significant urine output) and dialysis. Contributing conditions including hypertension and coronary heart disease should be evaluated and managed, as discussed separately. Evaluation for ischemia is indicated in patients with left ventricular (LV) systolic dysfunction who are candidates for revascularization as revascularization may improve ventricular function and reduce the risk for developing symptomatic or worsening HF. This is contingent upon the patient's estimated long-term prognosis and likelihood of clinical benefit from myocardial revascularization. (See "Overview of the management and prevention of heart failure in dialysis patients", section on 'General measures'.)
●For dialysis patients with HF
•Additional measures apply (eg, HF self-management, palliative services as appropriate) to all dialysis patients with HF. (See "Overview of the management and prevention of heart failure in dialysis patients", section on 'Additional general measures for HF'.)
•Specific measures to manage HF are indicated for the following groups:
-For patients with HF with reduced ejection fraction (HFrEF; LVEF ≤40 percent), treatment includes a combination of beta blocker and angiotensin converting enzyme (ACE) inhibitor (or angiotensin II receptor blocker [ARB]) therapy. For dialysis patients with HFrEF who have persistent symptoms of HF despite treatment with optimally titrated beta blocker plus ACE inhibitor therapy, the role of additional pharmacologic therapy is uncertain. For patients who can be closely monitored, some clinicians weigh the potential risks and benefits of addition of an ARB or mineralocorticoid receptor antagonist. (See 'Specific management of HFrEF' below.)
-For patients with HF with mid-range ejection fraction (LVEF 41 to 50 percent), we suggest management similar to that for HFrEF. (See 'Specific management of HFmrEF' below.)
-For patients with HF with preserved ejection fraction (HFpEF; LVEF >50 percent), general measures (particularly control of hypertension and volume status) are most important. The use of neurohormonal antagonists in this setting is controversial. (See 'Specific management of HFpEF' below.)
-In dialysis patients with arteriovenous access who have HF, consideration should be given to the possibility that high flow through the arteriovenous fistula is precipitating HF, particularly when fistula flows are high, cardiac output is increased, or right ventricular dilation and dysfunction develop [1-3]. In some cases, banding or modification of fistula flow can improve HF severity in these patients. (See "Evaluation and management of heart failure caused by hemodialysis arteriovenous access".)
-Patients with HF caused by valve disease that does not respond to medical therapy including optimizing volume status may require valve intervention (transcatheter or surgery), as discussed separately. (See "Valvular heart disease in patients with end-stage kidney disease".)
●For dialysis patients with LV systolic dysfunction (LVEF ≤40 percent) who do not have HF, specific measures apply. (See 'Specific management of asymptomatic LV systolic dysfunction' below.)
SPECIFIC MANAGEMENT OF HFrEF — Management of HF with reduced ejection fraction (HFrEF) in dialysis patient centers on the general measures described above, particularly adequate control of volume overload and pharmacologic therapy. Given the generally poor prognosis of patients in this setting, the role of cardiac resynchronization therapy is very limited in this setting. Management of refractory HF is discussed below. (See 'Management of refractory HF' below.)
Pharmacologic therapy for HFrEF
Approach to drug therapy for HFrEF — Our approach to drug therapy for HFrEF (left ventricular ejection fraction [LVEF] ≤40 percent) in the dialysis patient is similar to that for HFrEF in nondialysis patients, although there is only limited evidence to guide therapy in dialysis patients.
In the nondialysis patient, standard medical therapy for HFrEF includes diuretics as well as a combination of medications that have been demonstrated to improve survival in patients with HF without renal failure, including a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor (or an angiotensin II receptor blocker [ARB]), and in selected patients, a mineralocorticoid receptor antagonist (MRA).
There are limited data on use of these drugs in dialysis patients as described for the individual agents below. In addition, use of these agents in dialysis patients is complicated by the risk of exacerbating intradialytic hypotension, and for some of these agents, the risk of hyperkalemia. The initiation and titration of these agents can be challenging in hemodialysis patients, particularly those with low blood pressures. In general, the higher the predialysis resting blood pressure, the easier it is to uptitrate these agents. As an example, a dialysis patient with hypertension is a prime candidate for these agents since these drugs are effective antihypertensive agents and will therefore treat both HF and hypertension. In contrast, treatment of patients with chronically low blood pressures (eg, predialysis systolic blood pressures less than 100 mmHg) is challenging as these agents may not be well tolerated in the setting of dialysis. To avoid intradialytic hypotension, we may empirically modify dosing schedules, such as not administering these agents before dialysis on hemodialysis days.
●For dialysis patients with HF who have significant urine output, diuretic therapy is helpful to increase urine output and sodium excretion and decrease the need for volume removal with dialysis. Loop diuretics are the preferred choice in most circumstances given their greater potency compared with other diuretics. Dialysis patients receiving diuretics should be monitored for hearing loss and skin changes. Diuretics should be stopped when urine output becomes negligible. (See "Residual kidney function in kidney failure", section on 'Diuretics'.)
●For dialysis patients with HFrEF, we use combined beta blocker (carvedilol preferred) and ACE inhibitor therapy. An ARB is used in place of an ACE inhibitor in patients with a history of angioedema or ACE inhibitor-induced cough. (See 'Beta blockers' below and 'Angiotensin converting enzyme inhibitors' below and 'Angiotensin II receptor blockers' below.)
Data are lacking on which class of agent should be started first in dialysis patients, but we favor starting with the beta blocker, as the beta blocker carvedilol is the only drug demonstrated to improve survival in dialysis patients with HFrEF, although data are limited. In patients who tolerate the beta blocker, we suggest initiation of low-dose ACE inhibitor during the "middle" of the beta-blocker uptitration process. The ACE inhibitor (or ARB) and beta blocker should be uptitrated in tandem, with one drug change at a time. Slow uptitration of these agents is required in dialysis patients and is generally done at approximately every two- to three-week intervals, if tolerated. Slower uptitration may be necessary among patients who are chronically hypotensive (such as those with predialysis systolic blood pressures less than 100 mmHg). The rate of uptitration is determined empirically, given the difficulty in maintaining adequate blood pressures in some of these patients. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults", section on 'Dosing and cautions' and "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults".)
•Start low-dose carvedilol (eg, 3.125 mg twice daily) and titrate as tolerated to a moderate dose (eg, 12.5 mg twice daily).
•Add low-dose ACE inhibitor (eg, lisinopril 2.5 mg daily) and titrate as tolerated to a moderate dose (eg, lisinopril 20 mg daily). An ARB (eg, candesartan starting at 4 mg daily) is used instead of ACE inhibitor in patients with a history of angioedema or ACE inhibitor induced cough.
•Titrate carvedilol as tolerated up to target dose (25 to 50 mg daily).
•Titrate ACE inhibitor (or ARB if ACE inhibitor intolerant) as tolerated up to target dose (for ACE inhibitor, eg, lisinopril 40 mg daily; for ARB, eg, candesartan 32 mg daily)
●For dialysis patients with HFrEF who have persistent symptoms of HF despite treatment with optimally titrated beta blocker plus ACE inhibitor therapy, the role of additional pharmacologic therapy is uncertain. For patients who can be closely monitored, some clinicians weigh the potential risks and benefits of addition of an ARB or MRA. (See 'Uncertain role of ARB in addition to ACE inhibitor' below and 'Mineralocorticoid receptor antagonists' below.)
Of note, the combination of an ACE inhibitor, an ARB, and an MRA is generally avoided given the risk of hyperkalemia and the lack of evidence of efficacy.
●For most dialysis patients with HFrEF, we suggest not routinely using digoxin and reserve its use only for selected patients with atrial fibrillation who have not achieved adequate rate control with optimum beta blocker therapy and who can be closely monitored to maintain digoxin level <1.0 ng/mL. (See 'Digoxin' below.)
Dosing of each drug should be appropriate for renal failure. Issues surrounding the initiation of beta blocker therapy and the inability to reach the target dose with beta blocker therapy are discussed separately (see "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults"). Careful monitoring of serum potassium concentration must also be employed since the use of ACE inhibitors and ARBs has been associated with a significantly higher risk of hyperkalemia (defined as a predialysis serum potassium concentration of 5.5 mEq/L or higher). (See "Treatment and prevention of hyperkalemia in adults".)
A difficult question is how to optimally manage the hypotensive effects of these agents in chronically hypotensive patients. As previously mentioned, we may empirically modify dosing schedules to avoid intradialytic hypotension, such as not administering these agents before dialysis on hemodialysis days. In addition, blood pressure measurements may vary when assessed in different positions, particularly in the setting of peripheral arterial disease. The goal is to reduce central aortic pressure, which may be higher than brachial pressures if there is vascular stenosis present. (See "Hypertension in dialysis patients".)
Beta blockers — For dialysis patients with HFrEF (HF with LVEF ≤40 percent), we recommend use of beta blockers. We suggest carvedilol rather than other beta blockers in this setting, as carvedilol is the only beta blocker that has been studied in a randomized trial in this population. Also, based on limited observational data in dialysis patients (not limited to patients with HF), some have postulated that a poorly dialyzed beta blocker such as carvedilol may provide greater benefit than a highly dialyzable beta blocker (eg, metoprolol) [4,5]. This recommendation is consistent with the 2005 K/DOQI clinical practice guidelines [6]. Although data are lacking in dialysis patients, a reasonable alternative to carvedilol in this setting is bisoprolol or metoprolol succinate given evidence in patients not receiving dialysis; among dialysis patients, bisoprolol may be preferable given its lesser dialyzability.
Although the only randomized controlled trial of beta blocker therapy in dialysis patients with HF used an LVEF cutoff of <35 percent [7], in clinical practice we include patients with LVEF ≤40 percent based on indirect evidence from trials of patients with HFrEF without renal failure. (See "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Pharmacologic therapy'.)
A randomized trial in dialysis patients with HFrEF showed that beta blockers reduced the risk of death. In that trial, 114 dialysis patients with HFrEF (with LVEF <35 percent) were randomly assigned to carvedilol or placebo, in addition to standard therapy [7]. At two years, the mortality rate was significantly lower in the beta blocker group (51.7 versus 73.2 percent), as were the rates of cardiovascular death (29.3 versus 67.9 percent) and hospital admissions (34.5 versus 58.9 percent).
A retrospective study compared five-year mortality rates for 1700 hemodialysis patients with HF treated with a beta blocker (carvedilol, bisoprolol, and metoprolol controlled/extended release) with 1700 propensity-matched control patients with HF not treated with a beta blocker [8]. Information on LVEF was not available, so the percentages of patients with HFrEF and HF with preserved ejection fraction (HFpEF) were not identified. Mortality was significantly lower in the beta blocker group compared with the control group (39.2 versus 54.5 percent; adjusted hazard ratio [HR] 0.80; 95% CI 0.72-0.90). Subgroup analysis showed that patients receiving beta blocker plus renin-angiotensin system antagonist (ACE inhibitor or ARB) had the lowest mortality rate, while patients receiving neither beta blocker nor renin-angiotensin system antagonist had the highest mortality rate.
Beta blockers must be initiated at very low doses to minimize the risk of hemodynamic deterioration. This is particularly the case in patients who have intradialytic or sustained hypotension. (See "Overview of screening and diagnosis of heart disease in patients on dialysis" and "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults".)
Evidence on use of various beta blockers in HFrEF in the general population is available elsewhere. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults".)
Angiotensin converting enzyme inhibitors — We suggest ACE inhibitor therapy in dialysis patients with HFrEF. Direct evidence on the effect of ACE inhibitors in dialysis patients with HF is lacking, so this recommendation is based upon indirect evidence of benefit in patients with HFrEF with no or mild chronic kidney disease; ACE inhibitors have been shown in multiple randomized controlled trials to improve survival in patients with HFrEF and mild or no kidney disease [9,10]. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults", section on 'ACE inhibitor'.)
In contrast to patients with milder chronic kidney disease, there are only scant data on the use of ACE inhibitors in dialysis patients without HF. In the randomized Fosinopril in Dialysis (FOSIDIAL) trial, there was a nonsignificant trend toward fewer cardiovascular events with fosinopril compared with placebo among dialysis patients with LV hypertrophy [11]. Although clinical data are lacking, the favorable effects of ACE inhibitors on neurohormonal activation, hemodynamics, ventricular remodeling, and regression of LV hypertrophy may conceivably translate into a reduction in cardiovascular events in dialysis patients with LV dysfunction and HF [9,10].
The half-life and dialyzability of the ACE inhibitor should be taken into consideration in dosing in dialysis patients. Careful monitoring of serum potassium concentration is required, as a significantly elevated risk of hyperkalemia (defined as a predialysis serum potassium concentration of 5.5 mEq/L or higher) with ACE inhibitor use has been observed in dialysis patients [12]. (See "Overview of screening and diagnosis of heart disease in patients on dialysis".)
Angiotensin II receptor blockers — ARBs are used as an alternative to ACE inhibitor therapy for HFrEF in selected patients who cannot tolerate an ACE inhibitor. In addition, an ARB may be used in addition to ACE inhibitor therapy in dialysis patients with HFrEF with persistent HF symptoms despite optimal titration of beta blocker plus ACE inhibitor therapy.
ARB in place of ACE inhibitor — We suggest the use of ARBs in dialysis patients with HFrEF who are unable to take an ACE inhibitor due to angioedema or ACE inhibitor-induced cough. This approach is similar to that utilized in the general HF population. This recommendation is based upon evidence in patients with no or mild chronic kidney disease, showing that ARBs appear to be as or possibly slightly less effective than ACE inhibitors for treatment of HFrEF.
Direct evidence is lacking on the efficacy and safety of ARB therapy in dialysis patients with HF. As discussed separately, studies on the effects of ARB therapy on cardiovascular outcomes in dialysis patients have yielded mixed results [13-15]. In a meta-analysis of trials of ARB or ACE inhibitor therapy in dialysis patients, subgroup analyses found that ARB therapy was associated with lower cardiovascular events, as well as heart failure events, than other antihypertensive therapy or placebo [16](See "Hypertension in dialysis patients", section on 'Antihypertensive medications'.)
Uncertain role of ARB in addition to ACE inhibitor — The use of an ARB in combination with an ACE inhibitor in dialysis patients with HFrEF is controversial. For dialysis patients who have persistent HF symptoms despite optimum titration of beta blocker plus ACE inhibitor therapy, some clinicians evaluate the potential risks and benefits of adding an ARB (or MRA). The combination of an ACE inhibitor and ARB should be used with caution among hemodialysis patients because of the risks of hyperkalemia and intradialytic hypotension. Furthermore, the supporting evidence is from a single trial and awaits confirmation in other studies.
In a multicenter trial, 332 hemodialysis patients with HFrEF were randomly assigned to receive ARB or placebo in addition to ACE inhibitor therapy [17]. All patients were on an ACE inhibitor at the start of the trial, and 60 percent of patients were on a beta blocker. After a two-week run-in phase to test tolerance to the addition of telmisartan, drug dose was titrated to a target of 80 mg daily. A significant fall in mean systolic (125.3 to 118.3 mmHg) and diastolic (83.7 to 78.2 mmHg) blood pressure was observed during the first year in the telmisartan group. At a median follow-up time of 36 months, the addition of telmisartan was associated with a significant reduction in all-cause mortality (35.1 versus 54.4 percent; HR 0.51, 95% CI 0.32-0.82), cardiovascular death (30.3 versus 43.7 percent; HR 0.42, 95% CI 0.38-0.61), and HF-related hospital admissions (33.9 versus 55.1 percent; HR 0.38, 95% CI 0.19-0.51) compared with placebo. The study drug was discontinued because of adverse events in 27 patients (16.3 percent) who were taking telmisartan compared with 18 patients (10.7 percent) who were taking placebo; the most common cause of study drug discontinuation was hypotension. Hyperkalemia that required discontinuation of the study drug was observed in five patients (3 percent) who were taking telmisartan versus two patients (1 percent) who were taking placebo.
The results of the above trial in dialysis patients with HFrEF differ from the results of studies in two other groups of patients:
●For patients with HFrEF without end-stage kidney disease (ESKD), a meta-analysis of randomized trials (which included data from a much larger number of patients than the trial in dialysis patients) found that the addition of ARB to ACE inhibitor therapy significantly reduced hospitalization for HF but did not significantly change total hospitalizations, cardiovascular mortality, or total mortality compared with ACE inhibitor therapy alone. In addition, evidence supports the combination of MRA (rather than an ARB) and ACE inhibitor (along with beta blocker therapy) for selected patients with HFrEF without ESKD. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults", section on 'Evidence'.)
●The combination of ACE inhibitor plus ARB was associated with increased cardiovascular risk in a large observational study of hemodialysis patients with hypertension, in which a minority of patients had baseline HF [18]. Only about 25 percent of patients in this study had a baseline history of HF, and information on LVEF was not reported. The 701 patients taking the combination of an ACE inhibitor plus an ARB had increased risk of cardiovascular death (adjusted HR 1.45) compared with 1758 patients taking an ARB plus non-ACE inhibitor antihypertensive therapy. Patients taking an ACE inhibitor plus non-ARB antihypertensive agent were also at increased risk (adjusted HR 1.27) of cardiovascular death compared with the 1758 patients taking an ARB plus non-ACE inhibitor antihypertensive therapy. Further prospective, randomized, controlled studies are needed to clarify the clinical efficacy and safety of combination ACE inhibitor plus ARB therapy in dialysis patients without HF. Until additional studies are available, such combination treatment should be restricted to carefully selected patients with HFrEF.
Mineralocorticoid receptor antagonists — The use of MRA (eg, spironolactone, eplerenone) in dialysis patients with HF is controversial. For dialysis patients with HFrEF who have persistent symptoms of HF despite treatment with optimally titrated beta blocker plus ACE inhibitor therapy, some clinicians evaluate the potential risks and benefits of addition of an MRA (or ARB). (See 'Uncertain role of ARB in addition to ACE inhibitor' above.)
However, there is only limited evidence on the use of MRAs in dialysis patients (with or without HF). Low-quality evidence from randomized trials suggests that MRA therapy reduces all-cause mortality despite the risk of hyperkalemia [19]. Some evidence suggests that MRAs may be used without excessive risk of hyperkalemia in dialysis patients, but data are limited [20,21]. (See "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults", section on 'Evidence on MRAs'.)
MRAs impair renal potassium secretion and may decrease potassium excretion in the colon, as well as the translocation of potassium into tissues. Further evidence on the efficacy and safety of MRA therapy for dialysis patients with HFrEF is required. (See "Overview of the management and prevention of heart failure in dialysis patients", section on 'Uncertain role of mineralocorticoid receptor antagonist'.)
Digoxin — For most dialysis patients with HFrEF, we suggest not routinely using digoxin. In dialysis patients, we reserve use of digoxin for selected patients with atrial fibrillation who do not achieve adequate rate control by optimum doses of beta blocker and who can be closely followed to maintain a digoxin level <1.0 ng/mL. When digoxin is administered to a dialysis patient, dosing of digoxin should be adjusted for renal failure and close monitoring is required. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification" and "Cardiac arrhythmias due to digoxin toxicity" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy" and "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults".)
The use of digoxin in the dialysis population is challenging since the risk of digoxin toxicity may be higher than in individuals with normal kidney function. Among patients with HF without ESKD, data from clinical trials suggest that digoxin levels greater than 1.0 ng/mL are associated with an increased risk of death (see "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults"). Among dialysis patients, a retrospective cohort study also found that higher digoxin levels were associated with increased risk of death, particularly with lower serum potassium levels; the risk of mortality was significantly increased with a digoxin level ≥1.0 if predialysis levels of serum potassium were less than 4.3 mEq/dL [22].
Cardiac resynchronization therapy — Indications for cardiac resynchronization therapy (CRT) are discussed separately. The risk for device infection is increased among patients receiving dialysis through chronic indwelling catheters because of the risk for intermittent bacteremia. There is insufficient evidence regarding the use of CRT in dialysis patients with HF to support routine use, and decisions are made on a case-by-case basis [23,24]. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)
SPECIFIC MANAGEMENT OF HFmrEF — We treat dialysis patients with heart failure with mid-range ejection fraction (HFmrEF) with a combination of beta blocker plus angiotensin converting enzyme inhibitor (or angiotensin II receptor blocker) similarly to treatment of HFrEF in this population. This approach is based upon limited data on treatment of HFmrEF generally since data are lacking on treatment of HFmrEF in dialysis patients. (See "Treatment and prognosis of heart failure with mid-range ejection fraction".)
SPECIFIC MANAGEMENT OF HFpEF
Key management considerations — The mainstay of treatment of dialysis patients with HF with preserved ejection fraction (HFpEF) is control of volume overload using adequate ultrafiltration and treatment of contributing factors such as hypertension and myocardial ischemia. These general measures are discussed separately. There is little evidence to suggest benefit from beta blockers, angiotensin converting enzyme inhibitors, or angiotensin II receptor blockers in patients with HFpEF on dialysis, though these medicines are frequently used to manage other comorbid conditions in dialysis patients such as hypertension and coronary disease. (See "Overview of the management and prevention of heart failure in dialysis patients", section on 'Management of contributing conditions' and "Treatment and prognosis of heart failure with preserved ejection fraction".)
Role of MRA — There is indirect evidence that mineralocorticoid receptor antagonist (MRA) therapy may be useful in patients with HFpEF and preserved renal function. However, the role of MRA therapy in dialysis patients with HFpEF is controversial given the limited available evidence. For selected dialysis patients with HFpEF who can be carefully monitored, some clinicians perform an assessment of the potential risks and benefits of MRA therapy. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Mineralocorticoid receptor antagonists'.)
MANAGEMENT OF REFRACTORY HF — Given the poor prognosis generally associated with refractory heart failure (HF) in a dialysis patient, management includes assessment and discussion of prognosis with patients and their caregivers and treatment options including palliative care. (See "Palliative care for patients with advanced heart failure: Indications and systems of care" and "Palliative care for patients with advanced heart failure: Decision support and management of symptoms".)
Aggressive volume removal through optimization of dialysis is one of the most important considerations for patients with refractory HF (regardless of ejection fraction [EF]). Many patients remain undertreated and persistently hypervolemic, because it is challenging to achieve adequate ultrafiltration due to intradialytic hypotension or myocardial stunning [25]. For patients with refractory volume overload, we weigh options for more intensive dialysis, including more frequent but shorter daily dialysis and longer nocturnal dialysis regimens, since most of the signs and symptoms of HF are fundamentally related to the degree of volume overload [26,27]. If clinical euvolemia cannot be achieved despite these aggressive measures, persistent refractory volume overload can be an important consideration when exploring prognosis and goals of care with patients and their caregivers. While mechanical circulatory support with left ventricular assist device (LVAD) has been reported, the life expectancy for end-stage kidney disease (ESKD) patients treated with an LVAD is very limited (eg, 16 days compared with 2125 days for patients without ESKD) [28]. Therefore, LVAD is not considered a viable treatment option for patients with advanced HF with reduced EF (HFrEF) on dialysis.
Combined heart-kidney transplantation is an option for selected dialysis patients with refractory HFrEF. (See "Heart transplantation in adults: Indications and contraindications", section on 'Irreversible renal dysfunction' and "Heart transplantation in adults: Prognosis", section on 'Heart-kidney transplantation'.)
SPECIFIC MANAGEMENT OF ASYMPTOMATIC LV SYSTOLIC DYSFUNCTION — Pharmacologic intervention in the management of patients without end-stage kidney disease with asymptomatic left ventricular systolic dysfunction (ALVSD; defined for treatment purposes as LV ejection fraction [LVEF] ≤40 percent without HF) may delay the onset of HF, reduce the cardiac event rate, and improve survival. Data are lacking on the efficacy of therapy for ALVSD in dialysis patients, so recommendations for dialysis patients are based upon data in patients with normal or mild renal disease. Recommendations for therapy are based upon the severity of LV systolic dysfunction (ie, presence of LVEF ≤40 percent), as well as the cause of dysfunction (ie, post-myocardial infarction [MI] or other) (algorithm 1). (See "Management and prognosis of asymptomatic left ventricular systolic dysfunction", section on 'Neurohormonal blockade'.)
Pharmacologic treatment for ALVSD in patients on dialysis is similar to that for patients with or without chronic kidney disease not receiving dialysis (combination beta blocker therapy and angiotensin converting enzyme [ACE] inhibitor [or angiotensin II receptor blocker (ARB)]). An exception is that we prefer to start therapy with a beta blocker (rather than an ACE inhibitor or ARB) even in patients with no prior history of MI. For dialysis patients with ALVSD without prior MI, treatment with a beta blocker is based upon evidence from nondialysis patients and limited data in dialysis patients with HFrEF as discussed above (see 'Beta blockers' above). Beta blocker therapy is combined with treatment with an ACE inhibitor. An ARB is suggested as an alternative to ACE inhibitor for patients who have angioedema or an ACE inhibitor-induced cough. We generally start the beta blocker first and then add the ACE inhibitor (or ARB) next, as described above for dialysis patients with HFrEF. (See 'Approach to drug therapy for HFrEF' above.)
Many patients with ALVSD have had a prior ST elevation or non-ST elevation MI; standard indications for ACE inhibitor therapy and beta blocker therapy post-MI apply to these patients. We also recommend evaluation of ischemia as clinically appropriate, as discussed above. (See "Overview of the nonacute management of ST-elevation myocardial infarction" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction" and "Management and prognosis of asymptomatic left ventricular systolic dysfunction" and 'Approach to management' above.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis" and "Society guideline links: Heart failure in adults".)
SUMMARY AND RECOMMENDATIONS
●For all dialysis patients, a key general measure to manage or prevent heart failure (HF) is adequate volume control with loop diuretic therapy (if there is significant urine output) and dialysis. (See 'Approach to management' above.)
●For dialysis patients with HF with reduced ejection fraction (HFrEF; defined as HF with left ventricular EF ≤40 percent), the mainstays of therapy are treatment of volume overload and pharmacologic therapy including combined beta blocker and angiotensin converting enzyme (ACE) inhibitor therapy. An angiotensin II receptor blocker (ARB) is used in place of an ACE inhibitor in patients with history of angioedema or ACE inhibitor induced cough. (See 'Beta blockers' above and 'Angiotensin converting enzyme inhibitors' above and 'Angiotensin II receptor blockers' above.)
•For dialysis patients with HFrEF, we recommend beta blocker therapy (Grade 1B). We suggest carvedilol rather than other beta blockers in this setting (Grade 2C). Carvedilol is the only beta blocker that has been studied in a randomized trial in this population. Beta blocker therapy should be initiated at very low doses to minimize the risk of hemodynamic deterioration. (See 'Approach to drug therapy for HFrEF' above and "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults".)
•For dialysis patients with HFrEF who tolerate beta blocker therapy, we suggest adding ACE inhibitor therapy (Grade 2B). An ARB is used in place of an ACE inhibitor in patients with history of angioedema or ACE inhibitor -induced cough. (See 'Approach to drug therapy for HFrEF' above.)
●For dialysis patients with HFrEF who have persistent symptoms of HF despite treatment with optimally titrated beta blocker plus ACE inhibitor therapy, the role of additional pharmacologic therapy is uncertain. For patients who can be closely monitored, some clinicians weigh the potential risks and benefits of addition of an ARB or MRA. (See 'Uncertain role of ARB in addition to ACE inhibitor' above and 'Mineralocorticoid receptor antagonists' above.)
Of note, the combination of an ACE inhibitor, an ARB, and a mineralocorticoid receptor antagonist is generally avoided given the risk of hyperkalemia and the lack of evidence of efficacy. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults", section on 'Evidence'.)
●For most dialysis patients with HFrEF, we suggest not routinely using digoxin (Grade 2B). We reserve use of digoxin in this setting for selected patients with atrial fibrillation who have not achieved adequate rate control with optimum beta blocker therapy and who can be closely monitored to maintain digoxin level <1.0 ng/mL. (See 'Digoxin' above.)
●We treat dialysis patients with HFmrEF with a combination of pharmacologic agents similar to that for HFrEF. (See 'Specific management of HFmrEF' above.)
●The mainstay of treatment of patients with HFpEF on dialysis is treatment of volume overload, along with management of contributing factors such as hypertension and myocardial ischemia. The role of MRA therapy in dialysis patients with HFpEF is controversial given the limited available evidence. For selected dialysis patients with HFpEF who can be carefully monitored, some clinicians perform an assessment of the potential risks and benefits of MRA therapy. (See 'Specific management of HFpEF' above.)
●Pharmacologic treatment for asymptomatic left ventricular systolic dysfunction (ALVSD) in patients on dialysis is similar to that for patients with ALVSD not receiving dialysis (combination beta blocker and ACE inhibitor [or ARB]). An exception is that we prefer to start therapy with a beta blocker (rather than an ACE inhibitor or ARB) even in patients with no prior history of MI. (See 'Specific management of asymptomatic LV systolic dysfunction' above.)
