Device Therapy in Heart Failure Patients With Chronic Kidney Disease
Device Therapy in Heart Failure Patients With Chronic Kidney Disease
Device Therapy in Heart Failure Patients With Chronic Kidney Disease
STATE-OF-THE-ART PAPER
890
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
Abbreviations
and Acronyms
CKD chronic kidney
disease
CRT cardiac
resynchronization therapy
eGFR estimated
glomerular filtration rate
Figure 1
Mortality and Sudden Cardiac Death Across the Spectrum of Chronic Kidney Disease
Estimates of all-cause mortality (ACM) and sudden cardiac death (SCD) across the spectrum of chronic kidney disease (CKD)
and glomerular filtration rate (GFR) (background shaded curve) (2,15,40).
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
Figure 2
Risk factors common to both heart failure and chronic kidney disease
contributing to arrhythmogenesis, disease progression, and death (6,41,42).
891
Patients
Risk
Factors
With
for
ESRD
SCD
(16,18,23,43)
in for SCD in
Risk
Factors
Table 1
Patients With ESRD (16,18,23,43)
Primary Difference in
ESRD Patients
Cardiac structural
abnormalities
Dialysis procedure
Myocardial ischemia/stunning
Atheroma formation/progression
Induced interstitial fibrosis and
vascular endothelial
dysfunction
Rapid electrolyte changes
Alteration in cardiac
autonomic function
Prolonged QT appearance of
late potentials
Sympathetic overactivity
Other
Arterial hypertension
Increased rates of infection
CAD coronary artery disease; ESRD end-stage renal disease; LV left ventricular; LVEF left
ventricular ejection fraction; SCD sudden cardiac death.
892
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
Major
Supporting
Use in Patients
Heart Failure
and Reported
Renal
Characteristics
TableTrials
2 Major
TrialsICD
Supporting
ICD UseWith
in Patients
With Heart
Failure and
Reported
Renal Characteristics
Trial (Ref. #)
AVID (44)
n
1,016
Inclusion Criteria
Intervention
Renal Subgroup
Analysis
ICD vs.
antiarrhythmic
agents
NA
CAT (45)
104
NA
DEFINITE (46)
458
NA
MADIT-I (47)
196
MADIT-II (48)
1,232
704
ICD antiarrhythmic
agents
NA
2,521
MUSTT (49)
SCD-HeFT (50)
No
No
AVID Antiarrhythmics Versus Implantable Defibrillators; BUN blood urea nitrogen; CAT Cardiomyopathy Trial; DCM dilated cardiomyopathy; DEFINITE Defibrillators in Non-Ischemic
Cardiomyopathy Treatment Evaluation; EF ejection fraction; EP electrophysiology; ESRD end-stage renal disease; GFR glomerular filtration rate; ICD implantable cardioverter-defibrillator; IQR
interquartile range; LV left ventricular; MADIT Multicenter Automatic Defibrillator Implantation Trial; MI myocardial infarction; MUSTT Multicenter Unsustained Tachycardia Trial; NA not available;
NIDCM nonischemic dilated cardiomyopathy; NSVT nonsustained ventricular tachycardia; NYHA New York Heart Association; PVC premature ventricular complex; SCD-HeFT Sudden Cardiac
Death in Heart Failure Trial; VF ventricular fibrillation; VT ventricular tachycardia.
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
893
Major
Supporting
Use in Patients
Heart Failure
and Reported
Renal
Characteristics
TableTrials
3 Major
TrialsCRT
Supporting
CRT UseWith
in Patients
With Heart
Failure and
Reported
Renal Characteristics
Trial (Ref. #)
CARE-HF (51)
n
813
Inclusion Criteria
Intervention
Renal Subgroup
Analysis
COMPANION (33)
1,520
MADIT-CRT (52)
1,820
ICD CRT
No
MIRACLE (53)
453
369
1,798
ICD CRT
No significant difference
between GFR 60 or
60 ml/min/1.73 m2;
no further analysis
No significant difference
between GFR 82.7
ml/min/1.73 m2 or
82.7; no further
analysis
RAFT (55)
REVERSE (56)
610
CARE-HF Cardiac Resynchronization Therapy in Heart Failure; COMPANION Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure; CRT cardiac resynchronization therapy; HR
hazard ratio; ICM ischemic cardiomyopathy; MADIT-CRT Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy; MIRACLE Multicenter InSync Randomized
Clinical Evaluation study; NICM nonischemic cardiomyopathy; RAFT Resynchronization/Defibrillation for Ambulatory Heart Failure Trial; REVERSE Resynchronization Reverses Remodeling in Systolic
Left Ventricular Dysfunction trial; SCD sudden cardiac death; other abbreviations as in Table 2.
predictor of outcome. Despite this association, no differential benefit of the composite primary endpoint of all-cause
mortality or unplanned hospitalization for a major cardiovascular event was observed relative to renal function (/
median eGFR 60.3 ml/min/1.73 m2) (30). A retrospective
subgroup analysis of the Multicenter InSync Randomized
Clinical Evaluation study found that in patients with an
eGFR between 30 and 60 ml/min/1.73 m2, CRT improved
eGFR when compared with the non-CRT group (6.4 2.4
ml/min/1.73 m2 vs. 1.1 1.5 ml/min/1.73 m2; p
0.008) (31). No difference was observed in patients with
eGFR 60 ml/min/1.73 m2, and there were too few
patients with eGFR 30 ml/min/1.73 m2 to draw any
meaningful conclusions. This subgroup analysis was the first
large placebo-controlled trial to report an improvement in
eGFR with the use of CRT in patients with impaired renal
function. Another retrospective subgroup analysis of the
COMPANION (Comparison of Medical Therapy, Pacing,
and Defibrillation in Heart Failure) trial concluded that in
CRT candidates, the risk for SCD was significantly increased
by renal dysfunction (HR: 1.69; 95% CI: 1.06 to 2.69; p
0.03) (32,33). These findings are consistent with previously
identified increased risk of SCD in renal dysfunction.
Fung et al. (34) were among the first to identify a potential
association between impaired renal function and worse clinical
outcome among patients treated with CRT. They retrospectively evaluated echocardiographic assessment and renal function tests before and 3 months after CRT in 85 consecutive
patients. Mean baseline eGFR was reported to be 56.9 19.7
ml/min/1.73 m2. Successful left ventricular reverse remodeling
(LVRR), which they defined as a reduction of LV end-systolic
volume of 10%, was observed in 52% of patients after CRT.
They reported a small but significant improvement in eGFR in
those with LVRR when compared with those without at
3-month follow-up (2.5 7.0 ml/min/1.73 m2 vs. 13.1
11.9 ml/min/1.73 m2; p 0.001). Of significance, they also
demonstrated a marked deterioration in eGFR in those who
did not have LVRR (61.9 17 ml/min/1.73 m2 vs. 48.8
13.0 ml/min/1.73 m2; p 0.001). Change in eGFR after
CRT was significantly correlated with the changes in LV
end-systolic volumes, end-diastolic volumes, ejection fraction,
and mortality. Successful LVRR was the only independent
predictor of preservation of renal function after CRT. This
study indicated that changes in eGFR at 3 months after CRT
might clarify long-term prognosis in these patients. In addition, lack of significant LVRR after CRT may indicate a
high-risk group with potential for rapid decline in renal
function (34).
As for the role of CRT alone (without defibrillator
capacity) in patients with ESRD, there is not enough
894
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
Key
Questions
to ICD
and/or
Placement
Patients With
HF and With
CKD HF and CKD
Table
4 KeySpecific
Questions
Specific
to CRT
ICD and/or
CRTinPlacement
in Patients
1. What is the comparative effectiveness and safety in overall mortality across the strata of CKD patients who undergo ICD and/or CRT placement compared with those
who do not receive device therapy?
2. Is there a difference in the rates of sudden cardiac death by CKD status overall? If so, will the overall benefit improve with advancement in device therapy technology,
including less invasive devices?
3. What pharmacotherapies are most effective for reducing the risk of arrhythmic death in patients with HF and CKD?
4. Do any current or emerging renal protective therapies influence the risk of arrhythmic death in patients with HF?
5. What is the optimal timing of ICD or CRT-D implantation in patients with CKD?
6. Do current patterns of practice vary with regards to device therapy in this population and why?
7. What is the cost-effectiveness of ICD and/or CRT in patients with CKD and symptomatic HF?
8. How does device therapy affect quality of life in this population?
9. Can risk stratification models or risk scores facilitate device implantation decisions, particularly in terms of competing risks for mortality?
10. How can infectious risks and vascular access concerns be optimally addressed in patients with CKD and HF who undergo device implantation?
CKD chronic kidney disease; CRT cardiac resynchronization therapy; CRT-D cardiac resynchronization therapy defibrillator; HF heart failure; ICD implantable cardioverter-defibrillator.
Cannizzaro et al.
Device Therapy in HF, CKD, and ESRD
20.
21.
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