INTRODUCTION — Patients with end-stage kidney disease (ESKD) 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, left ventricular (LV) diastolic dysfunction (often associated with left ventricular hypertrophy [LVH]), arterial stiffness, LV systolic dysfunction, 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 general approach to management and prevention of HF in dialysis patients. Specific measures for various types of HF (HF with reduced ejection fraction [HFrEF] or HF with preserved ejection fraction [HFpEF]) are discussed separately. 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".)
ASSESSMENT OF CLINICAL STATUS — As discussed separately, all dialysis patients should undergo screening and evaluation for heart disease and cardiovascular risk. (See "Overview of screening and diagnosis of heart disease in patients on dialysis", section on 'Approach to screening and diagnosis'.)
The evaluation should address the following key questions, which relate to management and prevention of HF:
●Is HF present? HF is a clinical diagnosis based upon identification of a constellation of symptoms (eg, dyspnea and fatigue) that are caused by impairment of ventricular filling or ejection of blood (table 1). Thus, the clinical diagnosis of HF is limited to symptomatic (or previously symptomatic) patients and corresponds to stage C (structural heart disease with prior or current symptoms of HF) and stage D (refractory HF requiring specialized interventions) of the American College of Cardiology/American Heart Association (ACC/AHA) stages of HF (which also include stage A [at high risk for HF but without structural heart disease or symptoms of HF] and stage B [structural heart disease without current or prior signs or symptoms of HF]) [1]. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Stages in the development of HF'.)
•If HF is present:
-What type and cause of HF? (eg, HF with reduced left ventricular ejection fraction [HFrEF; LVEF ≤40 percent], HF with midrange ejection fraction [HFmrEF; LVEF 41 to 50 percent], or HF with preserved ejection fraction [HFpEF; LVEF >50 percent]). Common causes of HF in dialysis patients include ischemic heart disease and hypertensive heart disease. (See "Overview of screening and diagnosis of heart disease in patients on dialysis", section on 'Causes and risk factors'.)
-What is the patient's functional status? (See 'Functional classification' below.)
●Presence/absence of asymptomatic LV systolic dysfunction (LVEF ≤40 percent).
●Identification of contributing factors (eg, hypertension).
Functional classification — A classification system is required to monitor the functional status of patients with HF and to consistently apply clinical practice guidelines for treatment. General classification schemes for HF (such as New York Heart Association [NYHA] functional class) do not account for the dynamic/tidal nature of volume status in dialysis patients. A patient may have a higher (more severe) NYHA class before hemodialysis sessions compared with shortly after. A proposed functional classification scheme was developed specifically for patients with end-stage kidney disease (ESKD) by the Acute Dialysis Quality Initiative (ADQI) XI Workgroup [2].
The three elements of the proposed HF staging system for patients with ESKD are:
●Standardized echocardiographic evidence of structural and/or functional cardiac abnormalities (table 2)
●Dyspnea occurring in the absence of primary lung disease, including isolated pulmonary hypertension (ie, not due to elevation in pulmonary capillary wedge pressure)
●Response of congestive symptoms to renal replacement therapy (RRT)/ultrafiltration (UF)
The ADQI heart failure in ESKD classification system includes the following classes, ranging from least to most severe symptoms [2]:
●Class 1 – Asymptomatic patients with echocardiographic evidence of heart disease
●Class 2R – Dyspnea on exertion that is relieved with RRT/UF to a NYHA class I level
●Class 2NR - Dyspnea on exertion that CANNOT be relieved with RRT/UF to a NYHA class I level
●Class 3R – Dyspnea with activities of daily life (ADLs) that is relieved by RRT/UF to a NYHA class II level
●Class 3NR – Dyspnea with ADLS that CANNOT be relieved by RRT/UF to a NYHA class II level
●Class 4R – Dyspnea at rest that is relieved by RRT/UF to a NYHA Class III level
●Class 4NR - Dyspnea at rest that CANNOT be relieved by RRT/UF to a NYHA Class III level
The utility of the first element of the staging system (standardized echocardiographic evidence for cardiac abnormalities) was supported by a retrospective study of 654 patients who underwent echocardiography ≤1 month prior to or ≤3 months after initiation of hemodialysis [3]. Using the ADQI XI echocardiographic criteria, 87 percent of patients had at least one finding of structural heart disease. At 2 years, the mortality rate was 38 percent. Abnormal RV systolic performance was independently associated with death (HR 1.66, 95% CI 1.34-2.06).
OVERVIEW OF 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 largely apply. (See 'General measures' below.)
●For dialysis patients without HF with left ventricular systolic dysfunction (ALVSD; left ventricular ejection fraction [LVEF] ≤40 percent), specific measures apply. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of asymptomatic LV systolic dysfunction'.)
●For dialysis patients with HF:
•Additional general measures (eg, HF self-management, palliative services as appropriate) apply to all dialysis patients with HF. (See 'Additional general measures for HF' below.)
•Specific measures to manage HF are indicated for the following groups:
-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 receptor blocker [ARB]) therapy. Management of patients with persistent symptoms despite optimum titration of these medications is discussed separately. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFrEF'.)
-Patients with HF with midrange ejection fraction (HFmrEF; LVEF 41 to 50 percent), we suggest management with a combination of a beta blocker and an ACE inhibitor (or ARB). (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFmrEF'.)
-Patients with HF with preserved ejection fraction (HFpEF; LVEF >50 percent), general measures (particularly control of hypertension) are particularly important. For dialysis patients with HFpEF, the mainstay of therapy is management of contributing conditions (including optimizing volume status and control of hypertension). The use of a mineralocorticoid receptor antagonist (MRA) in this setting is controversial. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFpEF'.)
-Patients with valve disease with symptomatic disease who do not respond to medical therapy including optimizing volume status require valve intervention (transcatheter or surgery), as discussed separately. (See "Valvular heart disease in patients with end-stage kidney disease".)
GENERAL MEASURES — General measures for all dialysis patients to prevent or treat HF include monitoring for the development or worsening of HF and management of contributing or concurrent conditions (including hypertension, coronary heart disease).
Treatment goals — General measures to prevent or treat HF in dialysis patients are aimed at optimizing functional status and improving clinical outcomes (prolong survival and reduce cardiovascular event rates). However, there are limited data on the efficacy and safety of treatments or preventative measures for HF in dialysis patients. Optimal blood pressure and hemoglobin targets to reduce the risk of HF in end-stage kidney disease (ESKD) patients have not been established. There are limited data in patients with ESKD on therapies for HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤40 percent) that were established in patients with normal renal function or chronic kidney disease stage G3 or better. Evidence to guide management of HF with preserved ejection fraction (HFpEF; LVEF >50 percent) is limited even in patients with normal renal function; evidence for ESKD patients with HFpEF is even more limited, so it is even more difficult to formulate recommendations for this population. (See "Treatment and prognosis of heart failure with preserved ejection fraction" and "Overview of the management of heart failure with reduced ejection fraction in adults".)
While there is interest in left ventricular hypertrophy (LVH) regression as a surrogate outcome, available data have not established that specifically targeting LVH improves outcomes [4]. Observational data in dialysis patients suggest that progression of LVH is associated with increased risk of HF [5], cardiovascular death [6,7], and all-cause mortality [6,7]. In addition, observational studies suggest that the following measures that may improve clinical outcome also cause regression of LVH: control of hypertension, mineralocorticoid receptor antagonist (MRA) therapy, correction of anemia, more frequent hemodialysis, and kidney transplantation [4]. However, evidence is lacking that specifically targeting LVH improves clinical outcomes. (See "Treatment of anemia in patients on dialysis" and "Cardiovascular and renal effects of anemia in chronic kidney disease" and 'Uncertain role of mineralocorticoid receptor antagonist' below and 'Kidney transplantation' below.)
Monitoring — As discussed separately, all patients with ESKD maintained on dialysis should undergo screening for detection of symptoms or signs of HF and other heart disease. The functional classification of each patient should be assessed. (See "Overview of screening and diagnosis of heart disease in patients on dialysis", section on 'Screening and diagnosis of heart disease'.)
Dialysis patients with HF should be monitored by routine serial (eg, at least every month) review of symptoms and signs, functional classification, and medications. The frequency of monitoring by clinicians will need to be individualized based on factors such as clinical stability and duration of HF (ie, prudent to see patients more frequently with newly incident HF). Care should be taken to avoid drugs that may cause worsening HF (see "Drugs that should be avoided or used with caution in patients with heart failure"). Patients with worsening symptoms or signs of HF should undergo clinical evaluation with follow-up echocardiography as clinically appropriate.
Management of contributing conditions
Overview of contributing conditions — A number of conditions may contribute to HF in patients with ESKD; these conditions should be assessed and corrected, if possible. Conditions that may cause or exacerbate HF in patients with ESKD include the following:
●Volume overload. Renal failure with accompanying oliguria or anuria contributes to volume overload. (See 'Control of volume overload' below and 'Management of renal failure' below.)
●Hypertension. (See 'Control of hypertension' below and "Hypertension in dialysis patients".)
●Coronary heart disease. (See 'Management of coronary heart disease' below and "Clinical manifestations and diagnosis of coronary artery disease in end-stage kidney disease (dialysis)".)
●Anemia. (See 'Management of anemia and iron deficiency' below and "Evaluation and management of anemia and iron deficiency in adults with heart failure".)
●Atrial and ventricular arrhythmias occur in patients with HF and may cause or exacerbate HF (eg, atrial fibrillation with poor rate control may precipitate HF). (See 'Management of arrhythmias' below.)
Management of additional conditions that may cause or exacerbate HF in patients with ESKD is discussed separately:
●Valvular heart disease, particularly aortic stenosis (see "Valvular heart disease in patients with end-stage kidney disease")
●High-output states (eg, from shunting via the arteriovenous access) (see "Evaluation and management of heart failure caused by hemodialysis arteriovenous access" and "Clinical manifestations, diagnosis, and management of high-output heart failure" and "Causes and pathophysiology of high-output heart failure")
The following less common conditions contributing to HF in patients with ESKD are also discussed separately:
●Amyloidosis (see "Overview of amyloidosis" and "Amyloid cardiomyopathy: Treatment and prognosis" and "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis")
●Fabry disease, a rare disorder that is associated with multiple organ involvement, including renal failure and concentric LVH (see "Fabry disease: Cardiovascular disease")
Control of volume overload — A key component of therapy to prevent or manage HF in dialysis patients is treatment of volume overload with diuretic therapy (if there is significant urine output) and dialysis. Management of dialysis is discussed below. (See 'Management of renal failure' below.)
For dialysis patients with HF who have significant urine output, loop diuretic therapy is helpful to increase urine output and sodium excretion and decrease the need for volume removal with dialysis. 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".)
Management of renal failure — Management of renal failure in patients with ESKD includes identification and preparation of patients who require renal replacement therapy (RRT), choice of dialysis modality, optimizing the dialysis prescription, and identification of candidates for renal transplantation.
Modality — Patient preference (informed by the advice and guidance of the patient's nephrologist) should be a primary determinant of the modality choice for RRT. Dialysis options may include conventional thrice-weekly hemodialysis, peritoneal dialysis, or quotidian and/or long-duration hemodialysis. HF patients with ESKD may potentially benefit more from peritoneal dialysis than conventional thrice-weekly hemodialysis. Peritoneal dialysis avoids the risks associated with arteriovenous fistula creation and allows better control of volume status via daily ultrafiltration. While we believe all patients with HF should be evaluated for peritoneal dialysis, dialysis modality selection is based upon many factors including the patient's ability and willingness to perform peritoneal dialysis. In practice, patients with HF are often unable to perform peritoneal dialysis and lack the required support at home, so they frequently default to in-center hemodialysis. (See "Evaluation and management of heart failure caused by hemodialysis arteriovenous access", section on 'Prevention'.)
Optimizing dialysis prescription — Optimal management of dialysis includes optimizing volume status, optimizing the frequency and duration of dialysis, and additional measures to reduce the risk of intradialytic hypotension.
●Optimizing volume status is an important goal in the management of HF in hemodialysis patients. We agree with the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines that the maintenance of euvolemia is a major component of effective treatment in such patients [8]. Euvolemia may be defined as a state of normal biventricular filling pressures (ie, right atrial pressure and pulmonary capillary wedge pressure) or as the lowest filling pressure that can be achieved without compromising cardiac output, without significant extravascular fluid accumulation. Most nephrologists define euvolemia as the absence of clinical evidence of volume overload or volume depletion. In clinical settings, the term euvolemia is often used interchangeably with "being at the prescription target weight," which guides the amount of ultrafiltration to be achieved with each dialysis treatment. However, many patients (particularly those with HF) may be at the prescribed target weight but are not truly euvolemic. The optimal target weight is usually determined empirically by trial and error ("probing"). Using a trial-and-error approach, the target weight is set just above the weight at which unacceptable symptoms, such as cramping, nausea, vomiting, or hypotension, occur. For each patient, a pragmatic balance that minimizes risk of interdialytic hypervolemia and intradialytic hypovolemia is sought. (See "Intradialytic hypotension in an otherwise stable patient", section on 'Epidemiology and risk factors' and "Intradialytic hypotension in an otherwise stable patient", section on 'Prevention of recurrent episodes'.)
The definition of euvolemia (ie, optimal dry weight) and the approach to attaining this state in general hemodialysis patients are discussed separately. Although bioimpedance is used by some nephrologists to assess extravascular volume, its use is controversial, and we consider its role to be uncertain. (See "Hypertension in dialysis patients", section on 'Achieving optimal dry weight'.)
The fluctuating nature of fluid volume in relation to the hemodialysis schedule makes the maintenance of euvolemia difficult. In fact, anuric patients on chronic hemodialysis are practically never euvolemic because of the continuous interdialytic fluid gain and the acute intradialytic fluid removal. A balance between tolerability of hypovolemia and hypervolemia needs to be sought in individual patients. Many chronic hemodialysis patients are, however, chronically fluid overloaded, even immediately postdialysis. Efforts should be made to decrease target dry weight in these patients. In attempting to achieve postdialysis euvolemia in patients with ventricular systolic and/or diastolic dysfunction, hypotension during dialysis is a common and challenging problem, especially when interdialytic fluid gain is large. The screening echocardiogram enables assessment of intravascular and intracardiac volumes, ventricular function, and any valve disease. (See "Overview of screening and diagnosis of heart disease in patients on dialysis", section on 'Approach to screening and diagnosis'.)
In most clinical settings, filling pressures are not directly measured by invasive hemodynamic assessment, and instead noninvasive methods are used (eg, assessment of jugular venous pressure, peripheral edema, third heart sound, lung rales, and echocardiographic findings such as inferior vena cava diameter and collapsibility, E/e' ratio). When volume status can be accurately assessed by noninvasive assessment (which may include echocardiography), invasive hemodynamic assessment is not required. However, when the volume status of a patient remains uncertain (eg, if the patient has persistent HF symptoms despite apparently optimized volume status), referral to a cardiologist is suggested to evaluate the risks and benefits of invasive hemodynamic assessment. (See "Echocardiographic assessment of the right heart", section on 'RA pressure' and "Echocardiographic evaluation of left ventricular diastolic function in adults", section on 'Estimation of left atrial pressure'.)
●Optimizing the duration or frequency of dialysis. Greater duration or frequency of dialysis is an option for difficult-to-manage HF. Increasing the duration of hemodialysis or instituting daily hemodialysis is likely to provide better volume control and minimize intradialytic hypotension than that provided by a standard dialysis schedule. A randomized trial found that nearly daily dialysis (six sessions per week) reduced mortality rate as well as LV mass compared with conventional dialysis (three sessions per week), as discussed separately [9]. By contrast, studies comparing nocturnal (long nightly) hemodialysis with conventional dialysis have not demonstrated consistent effects on mortality or LV mass. (See "Short daily hemodialysis", section on 'Frequent Hemodialysis Network (FHN) daily trial' and "Outcomes associated with nocturnal hemodialysis".)
●Additional measures may help reduce the risk of intradialytic hypotension.
•A cool (35ºC) dialysate bath may reduce symptomatic hypotensive episodes by increasing both systemic vascular resistance and cardiac contractility. (See "Intradialytic hypotension in an otherwise stable patient" and "Intradialytic hypotension in an otherwise stable patient", section on 'Second-line approach'.)
•Managing the hypotensive effect of prescribed medications is challenging in chronically hypotensive dialysis patients. The most common (but not evidence-based) strategy is to alter dosing schedules on dialysis days, particularly withholding the dose before dialysis. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Pharmacologic therapy for HFrEF'.)
Kidney transplantation — Dialysis patients with HF require careful evaluation and management in determining whether they are candidates for kidney transplantation. While the presence of HF complicates the evaluation for kidney transplantation, observational studies suggest that kidney transplantation may improve LV systolic function and diastolic function and reduce LVH. Patients with end-stage heart disease who also have renal failure with an indication for kidney transplantation may be candidates for dual heart-kidney transplantation. Every effort should be made to exclude and treat any reversible causes of cardiac or renal dysfunction. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient" and "Heart transplantation in adults: Indications and contraindications" and "Management and prevention of heart failure in dialysis patients: Specific measures".)
Patients with HFrEF and ESKD are often not referred for kidney transplantation, because of concerns about risk of poor outcomes [10]. However, some data suggest that kidney transplantation may result in improved LV systolic function and improved survival in these patients. This was illustrated by a study of over 100 dialysis patients with HFrEF who underwent kidney transplantation between 1998 and 2002 [11]. There were no perioperative deaths. At 12 months, the mean LVEF increased from 32 to 52 percent, and more than two-thirds of patients achieved a LVEF of greater than 50 percent. Patients with normalized LVEF had significantly improved New York Heart Association (NYHA) class and lower risk of death or hospitalization for HF. However, patients with ejection fractions less than 30 percent did not typically normalize, and the heart function of those waitlisted 18 months or more did not improve.
Since ejection fraction can improve with medical therapy in some dialysis patients with HF, it is important to reassess possible eligibility for kidney transplantation after optimal medical therapy has been implemented. Thus, after evaluating and appropriately treating obstructive coronary artery disease, we reassess LV function at 12 weeks after the final uptitration of carvedilol among patients with a low ejection fraction. In our experience, a significant percentage of patients have an impressive rise in LVEF (ie, ≥10 ejection fraction points) after optimization of carvedilol and other medical therapies, and some are reactivated for the kidney transplant waitlist. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Pharmacologic therapy for HFrEF'.)
Kidney transplantation may also have a beneficial effect on cardiac remodeling as it is associated with regression of LVH [12-14]. As an example, one prospective study of 24 dialysis patients evaluated changes in LV mass by echocardiography at 3, 6, and 12 months posttransplantation [12]. There was a significant decrease in blood pressure at 12 months, and the incidence of LVH decreased from 75 to 52 percent. There was also a significant decrease in LV dilatation, and systolic dysfunction normalized in all patients after 12 months. It is unclear if removing the uremic milieu, improving blood pressure, or both were significant factors underlying these changes. Arterial stiffness also significantly improves after renal transplantation and may in part be responsible for the regression of LV mass [15].
Control of hypertension — Control of hypertension is a key intervention in preventing and managing HF in dialysis patients. The management of hypertension in dialysis patients includes gradual targeting euvolemia as well as administering antihypertensive medications as discussed in detail separately. Antihypertensive drug therapy is indicated for dialysis patients who remain hypertensive despite achieving optimal dry weight. (See 'Optimizing dialysis prescription' above and "Hypertension in dialysis patients".)
Goal blood pressure — Hypertension is an important contributor to HF. Elevated cardiac afterload increases can worsen congestion and impair forward output, even with mildly reduced systolic function [16]. Thus, we recommend treatment of hypertension in patients at risk for HF or with HF. For nondialysis patients at risk for HF or with HF, the goal blood pressure is 130/80 mmHg or less, as indicated in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) HF guideline update [17]. A target blood pressure is more difficult to define for dialysis patients given blood pressure fluctuations in predialysis, postdialysis, and home settings. Some experts suggest maintaining interdialytic self-recorded home blood pressure at less than 130/80 mmHg, but this recommendation is contingent upon patient tolerance. (See "Hypertension in dialysis patients" and "Goal blood pressure in adults with hypertension".)
Choice of therapy — The choice of antihypertensive agents should take into account their dialyzability, interdialytic fluid gain, propensity of the patient to experience intradialytic hypotension, interdialytic home blood pressure values if available, and other factors and therefore must be individualized. The choice of antihypertensive therapy varies depending upon whether HF is present and, if so, what type:
●For dialysis patients with an LVEF >50 percent with or without HF (see "Hypertension in dialysis patients"):
•In the absence of other specific indications, we suggest initial therapy with a beta blocker. Consensus is lacking on the choice of beta blocker in this setting as limited evidence is available to guide the choice of agent. Some clinicians prescribe carvedilol or labetalol in this setting, while others use atenolol. (See "Hypertension in dialysis patients".)
•If the beta blocker is not tolerated or is not sufficient to achieve target blood pressure, we add a dihydropyridine calcium channel blocker (eg, amlodipine).
•If the beta blocker plus calcium channel blocker is not sufficient, we add an angiotensin-converting enzyme (ACE) inhibitor. If an ACE inhibitor is not tolerated due to cough or angioedema, an angiotensin receptor blocker (ARB; candesartan or valsartan) is used.
●For dialysis patients with HFrEF (LVEF ≤40 percent), HF with midrange ejection fraction (HFmEF; LVEF 41 to 50 percent), or with asymptomatic LVEF ≤40 percent:
•We suggest initial therapy with a beta blocker. We prefer carvedilol to other beta blockers in this setting. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Beta blockers'.)
•If the beta blocker is not tolerated or is not sufficient to achieve target blood pressure, we suggest an ACE inhibitor. If an ACE inhibitor is not tolerated due to cough or angioedema, an ARB (candesartan or valsartan) is used. Given the lack of evidence on use of sacubitril-valsartan in dialysis patients, we do not use this agent routinely in this patient population.
•If maximum tolerated disease of beta blocker plus ACE inhibitor is not sufficient, we suggest adding a dihydropyridine calcium channel blocker (eg, amlodipine 5 to 10 mg daily).
The evidence supporting the choice and order of antihypertensive therapy is discussed separately. This includes an open-label, randomized trial that found that lisinopril compared with atenolol was associated with a higher risk of serious cardiovascular events and hospitalizations for HF among 200 hemodialysis patients with LVH and hypertension [18]. The study was terminated early at the recommendation of an independent safety monitoring board. A caveat of this trial is that blood pressure was higher in the lisinopril group, which complicates interpretation of results. Further, the sample size of this study was small, and the results have not been duplicated. (See "Hypertension in dialysis patients", section on 'Antihypertensive medications'.)
The available limited evidence on MRA therapy in dialysis patients has not established a consistent effect on blood pressure [19]. Evidence on MRA use in dialysis patients is discussed below. (See 'Uncertain role of mineralocorticoid receptor antagonist' below.)
Management of coronary heart disease — The treatment of coronary heart disease is aimed at relieving symptoms and improving outcomes. Management options include pharmacologic therapy (antithrombotic therapy, antianginal therapy, and treatment of anemia, hypertension, and other cardiovascular risk factors) and revascularization (percutaneous or surgical). In some cases, revascularization of obstructive coronary artery disease may improve systolic and diastolic ventricular function. Management of coronary heart disease is discussed separately. (See "Chronic coronary syndrome: Overview of care" and "Overview of the acute management of ST-elevation myocardial infarction".)
Management of anemia and iron deficiency — The management of iron deficiency and anemia is part of the routine care of dialysis patients. The management of iron deficiency in hemodialysis or peritoneal dialysis patients, including treatment targets and optimal modes of therapy, is discussed separately. We treat iron deficiency and iron deficiency anemia in dialysis patients with or without HF similarly, although data on treatment of iron deficiency in this population are lacking. (See "Treatment of iron deficiency in dialysis patients".)
Evidence on the use of intravenous iron in nondialysis patients with HF is discussed separately. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)
The use of erythropoiesis-stimulating agents involves a balance between avoiding symptomatic anemia and avoiding adverse outcomes from therapy to correct anemia. Although the presence of anemia is associated with increased mortality risk in patients with HF, it is uncertain whether anemia is associated with increased mortality or reflects more advanced disease and more extensive comorbidities. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure".)
We suggest targeting hemoglobin levels in the range of 10 to 11.5 g/dL, rather than higher levels, in most hemodialysis patients who are treated with erythropoiesis-stimulating agents. Although the literature is inconclusive, hemoglobin values that are between 10 and 12 g/dL (ie, hematocrit between 30 and 36 percent) appear to provide a better quality of life and perhaps better patient survival compared with values above this range. Target hemoglobin values for hemodialysis patients who are treated with erythropoiesis-stimulating agents are discussed elsewhere. (See "Treatment of anemia in patients on dialysis", section on 'Target levels'.)
Note that this recommendation for dialysis patients with HF differs from the recommendation to avoid erythropoiesis-stimulating agents in patients with HF without kidney disease. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'ESAs (not recommended)'.)
Management of arrhythmias — Cardiac arrhythmias may precipitate HF or be caused by HF.
Atrial fibrillation — Dialysis patients are at risk for developing atrial fibrillation with higher risk among those with older age, HF, or coronary heart disease. Patients with atrial fibrillation and HF may be treated with either a rate control or rhythm control strategy, although the subset of patients on dialysis are more commonly treated with rate control. For patients with atrial fibrillation and HF, a beta blocker is generally the primary agent for rate control. (See "The management of atrial fibrillation in patients with heart failure".)
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 (see "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Digoxin'). For this reason, for most dialysis patients with HF, we suggest not using digoxin; we reserve its use for selected patients with atrial fibrillation who do not achieve adequate rate control with optimum doses of beta blocker. When digoxin is used by a dialysis patient, dosing of digoxin should be adjusted for renal failure and levels followed very closely to maintain a digoxin level <1.0 ng/mL. (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", section on 'Digoxin'.)
Management of thromboembolic risk in patients with atrial fibrillation and chronic kidney disease is discussed separately.
Ventricular arrhythmias and sudden death — Dialysis patients (with and without HF) are at risk for ventricular arrhythmias and sudden cardiac death. Management of ventricular arrhythmias and risk of sudden cardiac death are largely the same in patients with and without ESKD, except for medication dosing adjustments for reduced glomerular filtration rate (GFR). Indications for implantable cardioverter-defibrillator (ICD) therapy for primary or secondary prevention of sudden cardiac arrest are the same as for patients with preserved renal function. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".)
Uncertain role of mineralocorticoid receptor antagonist — Low-quality evidence from randomized trials (limited by risk of bias and inadequate information size) suggests that MRA therapy in dialysis patients reduces all-cause mortality and cardiovascular mortality despite an increased risk of hyperkalemia. It has been postulated that MRA therapy may reduce the risk of HF through reduction in myocardial fibrosis and adverse remodeling, although an effect on risk of HF and a mechanism of action have not been established. We view the available evidence as preliminary and insufficient to support routine MRA therapy in dialysis patients. Some experts (including the 2015 International Society for Peritoneal Dialysis guidelines [20]), suggest MRA use to reduce mortality risk in selected dialysis patients; selection criteria include baseline serum potassium <5.0 mEq/L and compliance with careful monitoring of serum potassium.
Clinical trials to assess the efficacy and safety of MRA therapy in dialysis patients are underway [21,22].
A meta-analysis included nine randomized, controlled trials (seven placebo controlled) with a total of 829 adults receiving long-term hemodialysis or peritoneal dialysis [19]. Only the two smallest trials were limited to patients with HF. Most of the patients randomly assigned to MRA therapy were treated with spironolactone 25 mg/day; in two trials, some or all patients in the MRA group were instead treated with eplerenone 50 mg/day. Median duration of follow-up was six months. All-cause mortality was significantly reduced by MRA therapy (4.4 versus 12 percent; relative risk [RR] 0.40, 95% CI 0.23-0.69). Cardiovascular mortality was also significantly reduced (2.1 versus 7.1 percent; RR 0.30, 95% CI 0.15-0.75). There was a significantly increased risk of hyperkalemia with MRA therapy (4.7 versus 1.1 percent; RR 3.05, 95% CI 1.21-7.70). A later randomized, controlled trial in 253 dialysis patients without HF yielded similar results (reduction in all-cause mortality and cardio-cerebrovascular events) [23]. However, the clinical significance of these results is uncertain given limited trial quality and the low total number of events (59 total deaths in the meta-analysis; 12 deaths in the later randomized trial).
There is concern about the risk of hyperkalemia with MRA use, especially when used concurrently with ACE inhibitors or ARBs. MRAs impair renal potassium secretion and may decrease potassium excretion in the colon as well as the translocation of potassium into tissues. The risk of hyperkalemia was assessed in a noninferiority multicenter trial from Canada that randomly assigned 146 hemodialysis patients to 50 mg eplerenone or placebo [24]. At 13 weeks, there was no significant difference between groups in the rate of drug discontinuation due to hyperkalemia or hypotension (4 percent in the eplerenone group versus 2.8 in the placebo group). However, more patients in the eplerenone group developed hyperkalemia (11.7 compared with 2.6 percent in the placebo group). The effect of eplerenone on cardiovascular outcomes was not assessed in this trial.
However, the role of oral potassium binders to prophylactically mitigate the risk of hyperkalemia and facilitate the use of MRAs as a therapeutic strategy has been suggested but has not been tested in randomized, controlled trials. Both agents (patiromer and sodium zirconium cyclosilicate) have been shown to be efficacious for treating hyperkalemia. (See "Treatment and prevention of hyperkalemia in adults", section on 'Gastrointestinal cation exchangers'.)
Evidence for use of MRA therapy in dialysis patients with HF is discussed separately. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Mineralocorticoid receptor antagonists' and "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFmrEF' and "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Key management considerations'.)
ADDITIONAL GENERAL MEASURES FOR HF — The following are additional components of the general management of dialysis patients with HF:
●HF self-management – Dialysis patients with HF should be counseled on daily monitoring of weights (taking into account pre- and post-dialysis fluctuations), edema, and symptoms; medication management; and exercise. Dialysis patients with HF should receive dietary counseling including advice on maintaining adequate protein intake, fluid restriction, sodium restriction, and limiting foods high in potassium or phosphorus. Patients should also receive advice on smoking cessation and restriction of alcohol consumption and avoidance of illicit drug use (eg, cocaine). (See "Heart failure self-management", section on 'What constitutes appropriate self-care?' and "Patient education: Dialysis and diet (The Basics)" and "Nutritional status and protein intake in peritoneal dialysis patients" and "Protein intake in maintenance hemodialysis patients" and "Heart failure self-management".)
●Palliative care – As discussed separately, supportive palliative care services should be integrated into the care of patients with HF (including primary palliative care services as all HF patients and referral to secondary specialty palliative care as indicated). (See "Palliative care for patients with advanced heart failure: Indications and systems of care".)
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: Heart failure in adults" and "Society guideline links: Dialysis".)
SUMMARY AND RECOMMENDATIONS
●The cardiovascular evaluation of all dialysis patients should address whether heart failure (HF) is present, what type of HF is present (eg, HF with reduced left ventricular ejection fraction [HFrEF; LVEF ≤40 percent], HF with midrange ejection fraction [HFmrEF; LVEF 41 to 50 percent], HF with preserved ejection fraction [HFpEF; LVEF >50 percent], HF from other causes such as valve disease, presence/absence of asymptomatic LV systolic dysfunction [LVEF ≤40 percent]), and identification of contributing factors (eg, hypertension). (See 'Assessment of clinical status' above.)
●The approach to management or prevention of HF in the dialysis patient varies depending upon the clinical presentation.
•For all dialysis patients, most of the general measures to manage or prevent HF apply. (See 'General measures' above.)
•For dialysis patients without HF with LV systolic dysfunction (ALVSD; LVEF ≤40 percent), we suggest combined beta blocker and angiotensin-converting enzyme (ACE) inhibitor (or angiotensin receptor blocker [ARB]) therapy as tolerated, generally starting with a beta blocker. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of asymptomatic LV systolic dysfunction'.)
●For dialysis patients with HF:
•Additional general measures (eg, HF self-management, palliative services as appropriate) apply to all dialysis patients with HF. (See 'Additional general measures for HF' above.)
•Specific measures to manage HF are indicated for the following groups:
-Patients with HFrEF (LVEF ≤40 percent), treatment includes a combination of beta blocker and ACE inhibitor (or ARB) therapy. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFrEF'.)
-Patients with HFmrEF (LVEF 41 to 50 percent), we suggest management with a combination of beta blocker and ACE inhibitor (or ARB). (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFmrEF'.)
-Patients with HFpEF (LVEF >50 percent), general measures (particularly control of hypertension) are particularly important. For dialysis patients with HFpEF, use of a mineralocorticoid receptor antagonist (MRA) is controversial. (See "Management and prevention of heart failure in dialysis patients: Specific measures", section on 'Specific management of HFpEF'.)
-Patients with valve disease with symptomatic disease who do not respond to medical therapy including optimizing volume status require valve intervention (transcatheter or surgery), as discussed separately. (See "Valvular heart disease in patients with end-stage kidney disease".)
●General measures to prevent or treat HF in dialysis patients are aimed at optimizing functional status and improving clinical outcomes (prolong survival and reduce cardiovascular event rates). However, there are limited data on the efficacy and safety of treatments or preventative measures for HF in dialysis patients. While there is interest in left ventricular hypertrophy (LVH) regression as a surrogate outcome, the available data have not established that specifically targeting LVH improves outcomes. (See 'Treatment goals' above.)
•Control of hypertension is a key intervention in preventing and managing HF in dialysis patients. The management of hypertension in dialysis patients includes gradual targeting euvolemia as well as administering antihypertensive medications. The choice of antihypertensive therapy varies depending upon whether HF is present and, if so, what type. (See 'Control of hypertension' above.)
•Management options for coronary heart disease include pharmacologic therapy (antithrombotic therapy, antianginal therapy, and treatment of anemia, hypertension, and other cardiovascular risk factors) and revascularization (percutaneous or surgical), as discussed separately. (See "Chronic coronary syndrome: Overview of care" and "Overview of the acute management of ST-elevation myocardial infarction".)
•Management of anemia in dialysis patients (including those with HF) involves a balance between avoiding symptomatic anemia and avoiding adverse outcomes from therapy to correct anemia. (See 'Management of anemia and iron deficiency' above.)
•Management of renal failure includes optimizing dialysis prescription (including optimizing volume status and the duration and frequency of dialysis) and careful evaluation of the patient's candidacy for kidney transplantation. Maintenance of euvolemia is a major component of effective treatment in hemodialysis patients with HF. However, the fluctuating nature of fluid volume in relationship to the hemodialysis schedule makes the maintenance of sustained euvolemia difficult in hemodialysis patients. A practical balance between the avoidance of interdialytic hypervolemia and intradialytic hypovolemia must be sought individually. Patient with large interdialytic weight gain may benefit from increased frequency of hemodialysis. (See 'Management of renal failure' above.)
•Low-quality evidence from randomized trials suggests that mineralocorticoid receptor antagonist (MRA) therapy in dialysis patients reduces all-cause mortality and cardiovascular mortality despite an increased risk of hyperkalemia. We view this evidence as preliminary and insufficient to support routine MRA therapy in dialysis patients. Some experts suggest MRA use in selected dialysis patients; selection criteria include baseline serum potassium <5.0 mEq/L and compliance with careful monitoring of serum potassium. (See 'Uncertain role of mineralocorticoid receptor antagonist' above.)
