Does this dialysis-dependent patient have chronic heart failure or volume overload?

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease. (U S Renal Data System, USRDS 2010 Annual Data Report: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2010). The rate of events related to CVD increases exponentially with progressive decrease in glomerular filtration rate (GFR) and/or worsening albuminuria.

Despite recent advances in the management of chronic kidney disease (CKD) as well as advances in dialysis techniques and dialysis dose delivery, the pathophysiology of CVD in patients with CKD has remained elusive at best. Additionally, the spectrum of CVD in the growing population of CKD as well as dialysis dependent population is quite different than the spectrum of CVD in the general population. Notably, the major burden of CVD in CKD population is the development of chronic heart failure (CHF). Although the annual mortality rate while on dialysis is nearly 15-20%, 2/3 of these deaths are secondary to underlying and undiagnosed CHF and sudden cardiac death SCD.

Patients with different stages of CKD remain at increased risk for the development of symptomatic CHF. Dhingra et al demonstrated that incidence of CHF and composite end point of CVD death and heart failure increased with progression in CKD; incidence of CHF increased three fold /1000 person-years, such as in patients with estimated glomerular filtration rate (eGFR) >90 ml/min (3.2 / 1000 person-years) vs 8.9 /1000 person-years in patients with eGFR <60 ml/min. Similarly, the rate of composite end point (CVD death and heart failure) increased from 7.1 to 27.0 /1000 person-years, respectively. Detailed analysis of URDS data demonstrated that nearly 30% of incident dialysis patients have a history of CHF and another 7% will develop heart failure (HF) symptoms during the follow-up on dialysis therapy.

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The incidence of de novo coronary artery disease (CAD) is reported in only12% of ESRD patients during the mean follow-up of more than 3 years (hence an annual incidence of <4%). However, the survival (median) decreased by more than 50% in those with HF compared to those dialysis patients who did not have the diagnosis of CHF.

Heart failure (HF) in the general population as well as in patients with CKD is expected to become more prevalent given the ever-growing aging population. Its prevalence increases with declining renal function; the incidence of HF was 3-fold higher in individuals with an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2, compared with those with an estimated GFR ≥90 mL/min/1.73 m2.

Two distinct types of HF syndromes such as HF with reduced ejection fraction (HFrEF), also called heart failure due to systolic dysfunction (systolic HF) and HF with preserved ejection fraction (HFpEF), also called as diastolic HF. These two syndromes have similar clinical symptoms and signs, with different approaches to management and different responses to therapy whether present without or with CKD. In patients with CKD and clinical symptoms and signs of HF, more than 60% will have HF with normal or preserved EF (HFpEF). Although HFpEF is considered to be less enigmatic, however, recent data supports that its presence portends a bad prognosis that is similar patients with HFrEF.

HFpEF as well as HFrEF share many risk factors. However, history of long-standing hypertension, EKG abnormalities such as left ventricular hypertrophy, left atrial enlargement, left bundle branch block, and atrial fibrillation are more prevalent in patients with HFpEF. The median survival (2.1 years) and 5-year mortality of more than 70% in both groups (HPrEF or HFpEF) continues to remain a cause for concern. This prognosis is more sinister in CKD patients with HF. In dialysis patients however, the presence of HF at the start of dialysis is a strong and independent predictor of short-term and long-term mortality whether on HD or PD, and this mortality trend has remained unchanged during the past decade. The median survival of dialysis patients with baseline HF has been estimated to be 36 months, in contrast with 62 months for those without baseline HF. Over 80% of ESRD patients who are recently diagnosed with HF are expected to die within three years from the time of symptomatic HF.

The diagnosis of CHF in the dialysis population is confounded by the fact that the signs and symptoms of CHF as established by Framingham study overlap with the symptoms and signs of volume overload.

The presence of heart failure could be contributing to increased cardiovascular morbidity and mortality in dialysis patients. It is also possible, as has been demonstrated in the general population with CHF, that the presence of heart failure could be an important underlying morbidity that contributes to an increased rate of SCD in dialysis population.

However, whether a patient is labelled with CHF, pulmonary edema or volume overload, 5-year survival was 12.5, 20.2, and 21.3%, respectively. Recent data analysis supports the notion that inter-dialytic weight gain of >1.99 kg regardless of the diagnosis of heart failure is a risk factor for increased all-cause mortality as well as cardiovascular mortality. The mortality risk increases exponentially with an increasing degree of interdialytic weight gain.

Based on these observational data, it is prudent that dialysis patients who present with new onset dyspnea, or worsening shortness of breath (SOB), or sudden onset SOB (flash pulmonary edema like picture), or other symptoms and signs of volume overload should be evaluated for the potential diagnosis of acute decompensated heart failure.

What tests to perform?

Lab Testing

The diagnosis of CHF is based on symptoms, signs as well as the evaluation of different biomarkers based on American Heart Association (AHA) recommendations.

Cardiac biomarkers

The usefulness of different cardiac biomarkers in the diagnosis and management of acute heart failure in the general population is very well established. The recent introduction of the commercial assays for biomarkers such as B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) have a significant impact on diagnosis and treatment of acute dyspnea of unknown etiology as well as day to day management of heart failure in the general population.

There is an ongoing debate about the interpretation and significance of different levels of BNP and NT-proBNP in patients with CKD. It remains to be elucidated if increased levels of BNP and/ or NT-proBNP in the presence of CKD could be due to the combination of decreased clearance as well as increased production as a consequence of the almost universal presence of LVH in patients with CKD. If increased levels of BNP and NT-proBNP are in fact related to decreased clearance due to impaired renal function (although controversial), that may not allow these biomarkers to be used for prognostic purposes or to guide therapy of heart failure in the presence of CKD or on dialysis therapy.

However, a recent study by Anwaruddin et al demonstrated that using a cut off value for NT-proBNP (>1200 pg/ml) had a sensitivity (89%) and specificity (72%) for the emergency diagnosis of acute heart failure in patients with CKD (eGFR <60 ml/min/1.73 m2). Additionally, the magnitude of NT-proBNP level at the time of initial presentation in the CKD population correlated with 60-day all-cause mortality. Therefore, these biomarkers remain valid tools for the purposes of diagnosis and treatment in CKD population.

Changes (particularly a decrease) in the levels of these biomarkers with treatment of acute heart failure predicts all-cause mortality and hospital readmission rates in the general population. For example, a less than 50% drop in admission NT-proBNP was associated with greater risk of death or rehospitalisation at 1 year. The predictive value of decreasing levels of biomarkers has not been tested in patients with CKD.

Summary: despite the debate regarding the impact of renal clearance of biomarkers, the strong negative prognostic implications of a high NT-proBNP value in a dyspneic patient holds true even in patients with CKD.

Evaluation of underlying causes

Once the diagnosis of CHF is suspected, such patients should be evaluated for the underlying cause of CHF. Patients with CKD who present with more than one episode of shortness of breath, or pulmonary edema, or need repeated sessions of volume control (ultrafiltration) should be suspected of having acute heart failure or acute decompensated chronic heart failure.

Hospitalization for new onset shortness of breath provides an opportunity for comprehensive assessment, including history and physical examination, an electrocardiogram, cardiac biomarkers, echocardiography with doppler, and other goal-directed advanced testing based on the understanding that treatment of reversible factors for heart failure can be identified, investigated and treated as necessary.

Patients with CHF may have an underlying cardiac substrate leading to the onset of complex symptoms of heart failure. These substrates can range from obstructive coronary artery disease, viable but dysfunctional myocardium, valvular abnormalities, cardiac dyssynchrony, or pericardial disease.

Dysfunctional myocardium could be due to systolic dysfunction (systolic heart failure) or diastolic dysfunction (diastolic heart failure). Although diastolic dysfunction is the most common etiology of heart failure in patients with CKD, systolic heart failure is important to recognize since it could be due to underlying ischemic heart disease, leading to ischemic dilated cardiomyopathy.

A complete history and physical examination should be the first step in evaluating the patient with symptoms of heart failure. Specifically, it would allow identification of prior and current evidence of acute coronary events or structural heart disease.

The single most useful diagnostic test in the evaluation of patients with CHF is a detailed 2-dimensional echocardiogram in combination with Doppler flow studies to evaluate myocardium, including chamber dilatation, evaluation of heart valves and pericardium. According to ACCF/AHA guidelines, three elements need to be evaluated on echocardiographic examination: a) status of LV ejection fraction (EF): preserved or reduced; b) structure of LV; normal or abnormal; c) presence or absence of structural valvular disease, right ventricular or pericardial abnormalities.

Comprehensive echocardiographic evaluation allows definition of cardiac abnormalities, as patients oftentimes may have more than one cardiac abnormality that is responsible for the development of heart failure. Additionally, follow-up echocardiogram offers useful information regarding the changes (improvement or worsening, or development of new abnormalities) from baseline to assess the prognosis and gauge the response to therapy.

How to evaluate ischemic dilated cardiomyopathy?

Systolic dysfunction (LVEF < 50%) should be evaluated for underlying obstructive coronary artery disease for reversible ischemia (viable myocardium) by myocardial perfusion study (nuclear medicine) or dobutamine echocardiogram.

Noninvasive imaging to detect myocardial ischemia and myocardial viability is an important step in the evaluation of patients presenting with HF, since such patients can benefit by coronary revascularization. Patients with reversible ischemia shall be referred for coronary angiogram and if necessary for right heart catheterization unless the patient is not eligible for revascularization.

Endomyocardial biopsy

What is the role of endomyocardial biopsy (EMB) in the diagnosis and management of CHF in CKD population?

EMB remains controversial and opinion based. The role of EMB in the diagnosis of CHF in the general population has not been established. A recent guideline paper published by AHA reviewed different clinical scenarios based on the level of evidence about the role of EMB in the diagnosis of heart failure of different etiologies. Unfortunately, this position paper did not discuss the epidemic of CHF in the CKD and dialysis population. However, CKD patients with heart failure may be somewhat different than CHF patients in the general population.

After the diagnosis of CHF in the CKD population, the most important task is to determine the underlying pathophysiology of CHF.

Almost invariably patients with CKD have problems with volume control along with lack of response to diuretic agents. However, the challenge is to determine if the symptom complex is simply the reflection of underlying heart failure; systolic heart failure, diastolic heart failure, or high output failure, or the combination of these factors.

In patients with systolic heart failure, the most important challenge is to determine if systolic dysfunction is secondary to underlying epicardial coronary artery disease, which could be amenable to treatment with revascularization or due to uremic cardiomyopathy or other types of non-ischemic dilated cardiomyopathy as seen in the general population with heart failure.

Controversies in diagnostic testing for the evaluation of underlying ischemic myocardium (ischemic heart disease)

The optimal screening test (pharmacologic myocardial perfusion imaging or dobutamine (stress) echocardiogram) for the detection of obstructive coronary artery disease in patients with different degrees of CKD and in dialysis dependent patients is still debatable. However, institutional cardiology expertise is the main determining factor as to the type of modality to be used for the evaluation of the ischemic heart disease.

How should patients with heart failure or volume overload be managed?

Management of heart failure in CKD patients

Management of heart failure in the CKD population is a daunting task. Management of heart failure in the CKD population can be dichotomized based on CKD stage. Dialysis dependent patients with acute heart failure can be managed by aggressive ultrafiltation unless heart failure is associated with hemodynamic instability (MAP < 70 mmHg) or cardiogenic shock.

Such patients should be treated in the intensive care setting and considered for continuous renal replacement therapy (CRRT) based on the local hospital practices. The goal of the therapy is to relieve the symptoms and maintain the hemodynamic stability, and to evaluate the underlying pathophysiology and tailor the treatment for CHF.

Those patients with advanced CKD but not on dialysis can be treated with intensive diuretic therapy, but response to diuretics may not be optimal. Such patients are also at risk of developing acute kidney injury (AKI) due to cardio-renal phenomenon which may further confound treatment with diuretic therapy.

Medical therapy

According to AHA practice guidelines in the general population with heart failure: the following step-wise approach is based on the strong evidence accumulated by randomized controlled trials (RCTs) in the general population with heart failure. However, expert opinion calls for the treatment of HF in CKD and dialysis population with conventional therapies mostly based on the data extrapolated from the studies performed in the general population with heart failure.

There is a plethora of information indicating that HF in CKD and the dialysis population may have different pathophysiological bases, and patients with CKD have a distinct spectrum of drug metabolism with impaired renal clearance or different pharmacokinetics while on maintenance hemodialysis.

Step A

Evidence based studies support the initiation and dose-titration of ACE-I.

There is a lack of data regarding the efficacy and safety of ACE-I in patients with heart failure and concomitant CKD or dialysis therapy. Only a randomized study with the use of angiotensin-receptor blocker (telmisartan vs placebo) by Cice et al in a small number of dialysis patients with systolic heart failure showed that add on telmisartan on the background use of ACE-I, beta-blockers and digitalis resulted in more than 50% reduction in all-cause mortality in the treatment group.

Also, there was significant reduction in other primary end-points such as cardiovascular death, and HF length of stay with telmisartan therapy. The rates of hypotension and drug discontinuation due to other adverse events was not significantly higher with the use of telmisartan therapy despite forced telmisartan dose titration compared to the placebo group.

On the contrary, two large-scale, randomized studies with two different ARBs (Valsartan Heart Failure Trial and Candersartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) failed to show beneficial effect on all-cause mortality in the general population with heart failure. The results of telemisartan vs placebo in dialysis patients with heart failure are very encouraging, but need to be carefully applied in day-to-day practice. Post-hoc analysis of the Valsartan study (Val-HeFT) in the CKD population (eGFR <60) demonstrated persistence of benefit with valsartan in patients with mild CKD with heart failure.

Step B

Treatment with beta-blocker (particularly with carvedilol) decreases all-cause mortality as well as cardiovascular mortality in the general population with systolic heart failure. Only one study so far has demonstrated that carvedilol has a similar efficacy when used in dialysis patients with systolic heart failure even within the limitations of this study. These limitations include small sample size, single center study and a homogeneous Italian population. Data analysis of USRDS registry showed that the use of beta-blockers in dialysis population with heart-failure had an adverse effect on all-cause mortality.

Thus, the use of beta-blockers in the dialysis population should be individualized with careful monitoring of the dose titration and adverse outcomes that may not be inconsequential due to lack of data.

Treatment with carvedilol in patients with early CKD and systolic heart failure is associated with decreased mortality and heart failure hospitalizations. However, the safety and efficacy of carvedilol in heart failure patients with advanced CKD (stage 3b and above) could not be established.

Recent analysis and systematic review of all published studies with different types of beta-blockers in heart failure patients concluded that the use of these agents in CKD with heart failure reduced all-cause mortality with the caveat that there was a lack of people with CKD stage 3b and above in this data analysis.

Summary: the use of carvedilol or other beta-blockers in CKD and systolic heart failure is not supported by RCT but is simply being extrapolated from the data from the general population. In the absence of proven evidence, such therapy should be used judiciously and with careful monitoring.

Step C

Individualized need for digitalis therapy

AHA recommends that after optimizing the dose of beta blockers, ACE-I and diuretics, to further control the symptoms of HF, digitalis therapy may be initiated. The Digitalis Intervention Group established the efficacy of digitalis treatment in the general population with heart failure. Since digitalis is dependent on renal clearance, careful dose monitoring in patients with CKD is required. Secondary analysis of former study participants was stratified based on different stages of CKD and indicated that beneficial effects of digitalis persist in those with mild to moderate CKD. There is a paucity of data about the benefits of digitalis therapy in dialysis patients with systolic heart failure. Caution should be used in dialysis patients, with close monitoring of serum levels to avoid toxicity.

Step C

AHA recommends that blockade of aldosterone receptors either with the use of spironolactone or eplerenone, in addition to standard therapy, significantly reduces the risk of both morbidity and mortality among general population with severe heart failure. The safety and efficacy of aldosterone receptor blockers have not been demonstrated in patients with different degrees of CKD.

Isolated Ultrafiltration

Another consideration is the early use of isolated ultrafiltration when the patient continues to show symptoms of heart failure, very high levels of BNP, and/or NT-proBNP despite use of optimal pharmacological therapy. A recently completed randomized study (UNLOAD study) compared the short and long-term safety and efficacy of an advanced form of ultrafiltration therapy (Aquapheresis) versus conventional diuretic drug therapy in heart failure patients. This study demonstrated that 48 hours of aquapheresis resulted in significant reduction in weight loss (>30%) and net fluid loss (>28%) with corresponding decreased rates (more than 50%) for rehospitalization and decreased length of stay during the rehospitalization.

Another study called “The CARdiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF Study), is an NIH funded multicenter study to test the hypothesis that Aquapheresis therapy in hospitalized heart failure patients would result in better control of symptoms of heart failure and improvement in CKD compared to Stepped up pharmacologic therapy. (NCT00608491) It is not clear if aquapheresis therapy offers an added advantage in those heart failure patients who are already on three times per week maintenance hemodialysis therapy. Recent publication (2012) of this data suggested that use of ultrafiltration was not associated with added benefit but was associated with increased rate of adverse events. Hence the use of add-on ultrafiltration should be carefully considered.

Use of inotropes or nesiritide has not been studied in the CKD population and their use is being discouraged in the general population with heart failure.

Cardiac Resynchronization therapy (CRT) with Automatic Implantable Cardioverter-Defibrillator (AICD) Therapy

CRT: Patients with HFrEF often have non-synchronous ventricular contractions resulting in deficient ventricular filling, poor rate of increase in ventricular contractile force, mitral regurgitation, paradoxical septal wall motion, resulting in further reduction in cardiac output (CO) and associated with worsening of clinical symptoms of HF as well as increased all-cause mortality. Based on this hypothesis, during the past decade a plethora of RCTs demonstrated the benefits of CRT with the use of biventricular pacemaker device to facilitate the ventricular synchronization. Based on the multiple RCT and meta-analysis of patient-based data involving more than 4000 patients from different RCTs resulted in the development of guidelines for CRT therapy in patients with HFrEF and CRT eligible.

(Definition of CRT eligible patients include: HFrEF with NYHA class III-IV despite optimal medical therapy, LVEF ≤35% and QRS prolongation >0.12s).

AICD: Subsequently, a number of RCTs demonstrated that placement of automatic implantable cardioverter-defibrillator (AICDs) with CRT was associated with significant reduction in sudden cardiac death in HFrEF patients. Hence, guidelines were issued for the concomitant use of CRT-AICD for CRT eligible patients.

In the population with different stages of CKD or on dialysis therapy (ESRD) with HFrEF, most of the studies of CRT to complement the medical therapy and the use of AICD for the primary and secondary prevention of sudden death either excluded patients with CKD/ESRD or did not provide the data of baseline kidney function at the time of randomization. Thus, there is a paucity of data about the safety and effectiveness of CRT/AICD in the CKD and dialysis patient populations. Given the paucity of data, it is a daunting task for the clinicians to offer these therapies in such high-risk patient population who may perhaps benefit better than those without CKD given the extent and severity of their cardiovascular disease even in the absence of underlying HF syndrome.

Retrospective post-hoc analysis of the data from five different RCT such as CARE-HF, COMPANION, MIRACLE, RAFT and REVERSE demonstrated marginal benefits of CRT implantation in CKD patients. These subgroup results should be taken with a pinch of salt, given the limitations that each of these studies were not focused in the CKD patient population and each study had extremely small number of mild CKD (CKD stages I to II).

Retrospective sub-group analysis of the MIRACLE study (Multicenter InSync Randomized Clinical Evaluation study) evaluated CRT in HFrEF in CRT eligible patients and had randomized patients with serum creatinine level ≤ 3mg/dL at baseline. Post hoc analysis categorized patients in three eGFR subgroups (>90, 60-90, 30-60). Compared to the control group (no CRT), CRT use was associated with in improvement in LVEF and functional status, along with improvement in exercise capacity and the degree of mitral regurgitation. This subgroup analysis also demonstrated increase in eGFR in the baseline eGFR group 30-60 ml/min. This analysis sends a positive signal that perhaps CRT therapy should be considered in patients with eGFR >30 ml/min.

Friedman et al studied the comparative effectiveness of CRT with Defibrillator (CRT-D) versus Implantable cardioverter-defibrillator (ICD) in CRT-eligible patients with moderated-to-severe CKD, age 65 years and older with CKD (stage III to V) in the National Cardiovascular Data Registry (NCDR) ICD registry, comparing outcomes between two groups; CRT-D (n=9525) versus ICD only (n=1,421). Outcome data was derived from Medicare claims and censored at 3 years post-implantation for primary outcomes as HF hospitalization and death, and secondary outcomes such as device related complications, or progression to ESRD.

Among all the subgroups of CKD patients, use of CRT-D was associated with a significantly lower 3-year incidence of hospitalizations and death. The rate of progression to ESRD was similar in patients with Stage 3 and 4 CKD (n=10,348) with the use of CRT-D or ICD alone.

The major limitations of this study were that this was an observational retrospective study of only fee-based medicare patients, that it did not include the CKD patients who were CRT-eligible but did not receive the implant, and more importantly the cohort size with CKD 5 was less than 600 patients. Nonetheless, the study results support that perhaps CRT therapy does infer clinical benefit in moderate degrees of CKD (eGFR >30 ml/min).

One of the physiological variables that was demonstrated in the pivotal REVERSE study (In the Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction) was the concept of left ventricular reverse remodeling (LVRR) resulting in more than 10% reduction in left ventricular end-systolic volume as well as end-diastolic volume following CRT implantation. Subgroup analysis of REVERSE Study demonstrated that there was a significant interaction with the presence of CKD and LVRR, in particular less than 40% of patients with mild to moderate degrees of CKD showed LVRR compared to a rate of more than 60% without CKD.

Most importantly it is not clear if CRT therapy in CKD patients with HFrEF could have an impact on the progression in CKD. Two recent single center studies have suggested that use of CRT in advanced CKD (stages III and IV) in fact may have a beneficial effect both in the form of LVRR as well as improvement in CKD stage, though both studies are limited by small sample sizes.

Transvenous Implantable Cardioverter- Defibrillator therapy (AICD) in CKD and HF

The data on AICD benefit in different categories of CKD is mostly extrapolated from meta-analyses of RCTs, with different conclusions about the safety and effectiveness of preventing sudden cardiac death (SCD). It is fairly well established that the majority of deaths in patients with CKD are due to cardiovascular disease events (>40%) and more than 60% of these deaths are attributed to SCD, with an annual prevalence rate of 7% in the dialysis population.

During the past decade, seminal prospective RCTs demonstrated reduced all-cause mortality with ICD therapy for primary and secondary prevention of SCD in moderate HF patients. No prospective study data exists for the use of ICD therapy in patients with CKD and HF. Most of the RCTs for the use of AICDs either did not include patients with CKD or did not report the baseline kidney function. Evidence from the retrospective analysis of CKD subgroups in different studies have provided conflicting results about the safety and effectiveness of ICD therapy in these patients. For example: retrospective sub-group analysis of 60 pts with CKD enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II showed that ICD therapy resulted in survival benefit in each eGFR category of ≥ 35 ml/min and no benefit was seen in patients with eGFR <35 mil/min. On the contrary, a pooled patient-level analysis of MADIT-I, MADIT-II, and the Sudden Death in Heart Failure trial (SCD-HeFT) showed lack of survival benefit with ICD for primary prevention in patients with mild to moderate degrees of CKD.

Other retrospective observational studies by different investigators such as; Herzog et al (n= 6042), Charytan et al (n=11,160), and Hiremath et al (n=100) showed decrease in mortality in CKD patients with ICD therapy when used for secondary prevention. A subgroup analysis of 4 studies including patients with mild to moderate CKD had comparable mortality benefit with the use of ICD when compared to those without CKD.

Makki et al evaluated data of 5 observational studies (n=17460) that included CKD patients with ICD therapy for primary and secondary prevention (n=2854) and these were matched to CKD without ICD (n=14,606). It showed a reduction in all-cause mortality in CKD patients treated with ICD when compared with matched CKD controls not treated with ICD.

On the contrary when the data was analyzed to assess the effect of CKD on mortality in ICD patients treated for either primary or secondary prevention, it was astonishing that data showed increased mortality in the group of ICD patients who developed CKD versus those ICD patients who did not develop CKD.

A recent propensity-matched mortality analysis explored the survival benefit of ICD use for primary prevention of SCD in CKD patients with eGFR >60 ml/min. It demonstrated survival benefit ONLY for those with eGFR >30 ml/min. However, complications associated with the use of ICD were not reported.

Chen et al in a meta-analysis of several different types of studies that included RCT, ESRD patients with HF, Device therapy such as CR, CRT-D used to treat HF, and all the retrospective studies that included survival analysis, showed that both overall survival as well as 2-year survival was significantly better in CKD patients with ICD placement for either primary or secondary prevention when compared to those with CKD but not ICD.

Notwithstanding the results of all the above studies, two recent retrospective data analyses by Sakhuja and Hess showed that AICD use in CKD population is associated with poor outcomes. For example: Sakhuja et al evaluated 7 studies including 2516 patients found a staggering a 2.7-fold higher risk of mortality in ICD patients undergoing hemodialysis therapy when compared with those not receiving dialysis; Hess et al used National Cardiovascular Data Registry’s (NCDR) ICD registry and linked with the SS Death Master File [(total sample size=47,282, CKD (n=21,226) and without CKD (n=26,056)] defined by eGFR ≤60 ml/min and included patients on hemodialysis. All-cause mortality was 50% in patients with eGFR <30 ml/min or on dialysis within 3 years of ICD placement. The cumulative risk of increased mortality in patients on dialysis compared to non-dialysis advanced CKD patients (eGFR<30) was manifest during the first six months of ICD placement.

Complications associated with ICD placement in CKD patients

Several studies have demonstrated that dialysis patient are at increased risk for device-related complications particularly hematoma and infections are significantly more common in dialysis patients. Central vascular access is a cause for concern as patients remain at risk for lead-related stenosis as well as thrombosis. There is an ongoing evaluation of implantation of the subcutaneous ICD system, which could reduce the device-related complications in dialysis population.

Current status of CRT and ICD placement in patients with different stages of CKD

At present more robust studies are needed to establish the safety, efficacy and cost-effectiveness of CRT and ICD therapy in patients with advanced CKD (eGFR<30 ml/min) and specifically those on dialysis and with HFrEF. The ongoing Implantable Cardioverter Defibrillation study for the efficacy and safety of prophylactic transvenous ICD therapy in dialysis patients (ICD 2) trial: a prospective randomized study of the efficacy and safety of prophylactic ICD therapy in the reduction of SCD is being completed and may be reported in 2017-2018. At present given the complexity of signals from the retrospective data analysis either with CRT or ICD placement in dialysis population with HF, we need to have a detailed and balanced discussion regarding the individual risk and benefit to assist our patients to make an informed choice about the use of these devices.

Mechanical device, heart transplantation, or palliative therapy

The AHA states that CHF patients who continue to remain symptomatic after optimization of medical therapy, or need inotropic support, should be considered for mechanical device or heart transplantation.

A ventricular assist device (VAD) can be used for those with failure of response to medical therapy and who are hospitalized with end-stage systolic heart failure. It can be used as a bridge-to-transplant or as a destination therapy for providing a long-term support in patients who are not candidates for heart transplant.

Without this device, there is a greater risk of death during the wait for a transplant. When used as a bridge-to-transplant or as destination therapy, the VAD provides effective hemodynamic support, maintains or improves other organ function, improves exercise performance and enables participation in cardiac rehabilitation.

Given the benefits of VAD therapy in the population with CHF, there is a limited experience with the use of VAD in patients with heart failure and different stages of CKD or dialysis therapy. Some studies have suggested that renal failure of any degree is a major contraindication for treatment with VAD. Nonetheless, a small retrospective study in patients with heart failure, cardiogenic shock and advanced renal failure demonstrated reversal of AKI when treated with LVAD.

Challenges of treatment in dialysis patients with CHF

Dialysis patients with systolic heart failure pose a complex problem in dialysis units due to; a) baseline hypotension as well as increased risk of developing intradialytic hypotension, b) difficulty in controlling the weight due to inadequate UF, c) frequent hospitalizations due to symptoms of heart failure, d) serial decrease in LVEF due to perhaps ongoing myocardial damage. This group of dialysis patients pose different types of challenges for the providers as well as the dialysis unit staff.

Can such patients be treated with peritoneal dialysis therapy?

Peritoneal dialysis (PD)

Advocates of PD have suggested that PD therapy could prevent hemodynamic fluctuations and prevent IDH. However, observational studies, as well as a recently reported prospective study with a follow-up of nearly 4 years demonstrated that mortality is in fact higher in patients with systolic heart failure on PD. In view of this evidence, dialysis patients with systolic heart failure may not benefit by PD or switching from IHD to PD therapy.

Short daily hemodialysis (SDHD)

This modality consists of 1.5 -2.5 hours of daily dialysis for 5-6 days per week. SDHD has the advantage of regulating the volume control on a daily basis with effective reduction in ECF volume excess and without need for forced UF to achieve volume control. It definitely abrogates IDH. Hence, SDHD should be a preferred modality of dialysis in patients with systolic heart failure and recurrent symptoms of heart failure. Furthermore, SDHD reduces the left ventricular mass index (LVMI).

Nocturnal home hemodialysis (NHD)

Nocturnal hemodialysis patients are trained to provide treatments in their home 6 or 7 nights per week for 3 to 8 hours per treatment. The most important advantage of NHD therapy has been associated with cardiovascular benefit, among the most important CV benefit is the regression of LVMI as has been demonstrated by observational study as well as by randomized study. Additionally, NHD has also been demonstrated to lead to an increase in LVEF in patients with systolic heart failure.

Kidney transplantation: Should dialysis patients with systolic heart failure with reduced LVEF be considered for kidney transplantation?

More often than not dialysis providers believe that dialysis patients with chronic heart failure and reduced LVEF are poor candidates for kidney transplantation. Also, it is often argued that such patients should be considered for the combination of kidney and heart transplants.

Evidence suggests that systolic heart failure and reduced LVEF can reverse to normal LVEF with resolution of symptoms of heart failure after successful kidney transplantation. These studies support the hypothesis that most of the dialysis patients with heart failure and reduced LVEF could have uremic cardiomyopathy.

How to utilize team care?

Specialty consultations: Dialysis patients with symptoms of shortness of breath that persists after achieving approximate dry weight should be screened for signs of heart failure. A two dimensional echocardiogram should be obtained.

Nurses Dialysis nurses should offer patients with chronic heart failure dietary guidance including low salt diet with adequate protein intake based on their nutritional status.

Dietician: Chronic heart failure often leads to poor protein intake due to poor appetite leading to cardiac cachexia. These patients benefit from intensive dietary interventions.

Therapists (physical, occupational, speech, other): Dialysis patients with chronic heart failure will benefit from a cardiac rehabilitation program.