**Effectiveness of Ultrafiltration in Patients with Congestive Heart Failure**

Luai Alhazmi, Abdulelah Nuqali, Ankush Moza and Mujeeb Sheikh

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63393

#### **Abstract**

Among all cardiac diseases, congestive heart failure (CHF) is the leading cause of patient rehospitalization. Fluid overload and lung congestion are the major reasons for these recurrent admissions. This disease can be associated with worsening renal function, a phenomenon called cardiorenal syndrome (CRS), which is challenging to manage. Conventional diuretic therapy of both CRS and diuretic resistance has offered limited efficacy. Compared with conventional therapy, hemodiafiltration (HDF) has shown promising results for fluid removal in some clinical trials, with inconclusive effects on all-cause mortality and rehospitalizations. Nonetheless, the results are inconsistent because of the high heterogeneity among these studies. In this chapter, we shed light on the role of different methods of ultrafiltration, including peritoneal ultrafiltration, sustained slow efficiency dialysis, and HDF, in the management of CHF, and review the current literature.

**Keywords:** congestive heart failure, cardiorenal syndrome, peritoneal ultrafiltration, sustained low efficiency dialysis, hemodiafiltration

#### **1. Introduction**

Congestive heart failure (CHF), sometimes called chronic heart failure or simply heart failure, is a disease that affects a patient's everyday life and can have deleterious effects on both physical and mental well-being [1–3]. Patients with CHF have a worse health-related quality of life than those with many other chronic diseases, such as chronic obstructive pulmonary disease, hypertension, diabetes mellitus, and myocardial infarction [3, 4]. Moreover, rehospitaliza‐

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tions are a major concern among these patients, their families, and their health service provid‐ ers. CHF causes the highest rehospitalization rate among all chronic diseases, reaching up to 27% [5]. Patients with CHF have a poor prognosis, with a 1-year survival rate that is compara‐ ble or worse than that for common neoplasms such as prostatic or breast malignancies. Stewart et al. showed that the median survival time for patients with CHF was 16 months with 25% 5 year survival rate [6, 7]. Despite all advances in the management of CHF, it is still the leading cause of mortality among cardiac diseases [8, 9]. Fluid overload and lung congestion are the most recurrent cause of admissions in these patients [10]. Almost 50% of them are discharged with residual congestion, and most rehospitalizations occur in patients who are diuretic resistant [11]. Diuretic resistance, in which patients with CHF have reduced diuresis and natriuresis in response to diuretics, causes higher mortality and rehospitalizations [10, 12, 13]. CHF is also associated with cardiorenal syndrome (CRS), a condition in which renal function worsens and is challenging to manage [14]. Conventional diuretic therapy of both CRS and diuretic resist‐ ance has shown limited efficacy with no robust data on efficacy in terms of well-designed randomized clinical controlled trials [15, 16]. However, hemodiafiltration (HDF), isotonic fluid replacement through positive hydrostatic pressure, has recently emerged as an alternative or last resort for these complex patients. The aim of this physiological approach is to decrease neurohumoral activation, which in turn curbs the vicious cycle leading to cardiac and renal insult [17, 18]. Some promising results have been reported in initial studies, but the data conflict and are inconclusive. As a result, no clinical guidelines to date have adopted HDF as an alternative to diuretic therapy [10, 19–22].

#### **2. Diuretic resistance and CRS syndrome**

No specified definition is available for diuretic resistance, as it is the outcome of treatment and not a pathological condition in itself. The efficacy of loop diuretics can be evaluated as a measure of urine output, change in weight, and balance in net fluid [23]. Patients unable to meet their needs for decongestion despite high doses of loop diuretics are generally labeled as diuretic resistant. Some current studies have reported the efficacy of diuretics in terms of clinical outcomes in patients with CHF [24–31]. Although these studies used different methods and metrics, the outcomes were similar in all: patients with diuretic resistance showed poor outcomes compared with those without diuretic resistance. Even after correcting for glomer‐ ular filtration rate (GFR), a strong correlation between worse clinical results and diuretic resistance was observed, showing that the efficacy of diuretics and the GFR each have a different impact on clinical outcomes. GFR is a good indicator of the kidney's clearance ability. When this rate is normal, the renal tubules are able to maintain homeostasis of electrolytes and euvolemia. Even if the GFR is reduced to up to 20 mL/min, usually 28.8 L of fluid is filtered, and sodium excretion is about 4000 mEq. The metrics used in current studies for diuretic efficacy are indirectly related to the effectiveness of loop diuretics for sodium excretion. Consequently, these metrics indicate a better prognosis than does the GFR in terms of the kidneys achieving euvolemia.

Several studies that used different metrics tried to establish a correlation between efficacy of diuretics and heart failure-related clinical outcomes. In the case of patients having reduced diuretic efficacy, Testani et al. [24] found high mortality rates even after correcting for diuretic dose and fluid output. Valente et al. [25] and Voors et al. [31] observed increased death and rehospitalization rates associated with diuretic resistance in heart failure at 60 days, whereas Ter Maaten et al. [28] reported similar outcomes at 30-day follow-up. After correcting for the GFR, Verbrugge et al. [29] and Singh et al. [26] reported higher death and rehospitalization rates related to diuretic resistance.

On the contrary, CRS is a condition that becomes apparent from a decrease in the GFR and acts as a barrier to the treatment of CHF by limiting the renal function [32]. At first, a decrease in blood flow in the kidney was considered to cause a low GFR, but recently a number of studies have shown that cardiorenal interactions have several complex mechanisms, some of which may be reversible. In a commonly used classification given by Ronco and colleagues [33], CRS is grouped into four types: type 1 is characterized by acute heart failure, leading to acute kidney injury; type 2 involves chronic cardiac impairment such as CHF, resulting in chronic kidney disease; type 3 is a result of primary kidney function impairments, resulting in acute cardiac impairment that may become evident as heart failure; and type 4 involves chronic cardiac impairments influenced primarily by primary chronic kidney disease such as uremic cardiomyopathy. A further type 5 CRS involves systemic disorders of the chronic or acute type such as sepsis; diabetes causes both cardiac and renal dysfunction.

Acute CRS is a reflection of worsening renal function in patients with CHF [34]. CRS is found in 25–33% of all patients with acute decompensated heart failure (ADHF) [35, 36]. Extrarenal hemodynamic changes, cellular dysregulation, neurohormonal activation, and intrarenal microvascular and oxidative stress underlie acute CRS [34, 37]. In a few cases, intravenous diuretic-mediated renal injury is responsible for worsening renal function [16, 38, 37]. Other proposed mechanisms of CRS pathophysiology include neurohumoral adaptations, reduced renal perfusions, elevated venous pressure, and dysfunction of the right ventricle [39, 40].
