Arrhythmia in Patients with Chronic Kidney Disease

بسم الله الرحمن الرحيم

"وقل رب زدني علما "

Arrhythmia in patients with chronic kidney disease

Done by

Ali JabbarMakki

AkramAbdul-Hassan Azeez

Supervised by

Dr. Majeed Mohan Al-Hamamy

Dr. DheaaKhalaf Al-Omery

Abstract

Visiting to CCU of Al-Hussian teaching hospital three times per day to collect the the appropriate information from the patients who are admitted to the CCU searching about the link between Chronic kidney disease with any type of arrhythmia

Introduction

Cardiac arrhythmias are disturbances in the rhythm of the heart, manifested by irregularity or by abnormally fast rates (tachycardias) or abnormally slow rates (bradycardias).Patients who perceive these abnormalities most frequently observe palpitations, which some describe as the sensation of ‘my heart turning over in my chest’, or awareness that their hearts are beating rapidly or slowly. Other symptoms include weakness, shortness of breath, lightheadedness, dizziness, fainting (syncope) and, occasionally, chest pain. The symptoms tend to be more severe when the rate is faster, the ventricular function is worse, or the arrhythmia is associated with abnormalities of autonomic tone. However, many patients with arrhythmias report no symptoms, and the condition may first be discovered during a routine examination. A tachyarrhythmia that is rapid enough and lasts long enough can produce cardiomyopathy and congestive heart failure. in these cases, treatment of the arrhythmia can often return normal function to the ventricles. Although certain physical signs present during arrhythmias can help the physician make a correct diagnosis, electrocardiography is the standard method used for recognizing cardiac arrhythmias. A prolonged electrocardiographic recording, often called a ‘Holter monitor’, or an event recorder that the patient activates when sensing an abnormality, may assist in confirming the diagnosis when the arrhythmia occurs sporadically.

Chronic kidney disease

(CKD) is a long term condition caused by damage to both kidneys.Thereis no single cause and the damage is usually irreversible and can lead to ill health. In somecases dialysis or transplantation may become necessary. It is only relatively recently that theepidemiology of CKD has been studied in detail with the finding that it is more common thanpreviously thought. Diabetes mellitus, which is alsobecoming more common, is one cause of CKD. Chronic kidney disease is seen more frequentlyin older people and therefore is likely to increase in the population as a whole.People with CKD are at higher risk of cardiovascular disease and they should be identifiedearly so that appropriate preventative measures can be taken. In the early stages of CKD peoplemay be unaware that they have any illness and a blood or urine test may be the only way itis discovered. Establishing which conditions predispose to CKD identifies those who shouldhave the necessary blood or urine tests. Early detection of CKD can establish if kidney diseaseis likely to be progressive allowing appropriate treatment to slow progression.End-stage renal disease, also called established renal failure, is chronic kidney disease whichhas progressed so far that the patient’s kidneys no longer function sufficiently and dialysis ortransplantation become necessary to maintain life. Given the increased recognition of CKD atearlier stages, the risks of cardiovascular disease and the potential for the disease to progresstowards ESRD, guidelines for early identification and management of patients are now a priority.

PATHOPHYSIOLOGY

CAD is likely to be at least in part responsible for arrhythmias in CKD. There are a number of reasons why CKD patients will have an increased risk of CAD. The pathological processes that cause CAD are also likely to lead to CKD. For example, chronic hyperglycaemia and insulin resistance in diabetes mellitus can cause endothelial dysfunction and subsequent atheroma formation in all asculature. It is likely that the proteinuria seen in diabetic nephropathy, a marker of adverse outcome, is an early vascular effect of endothelial dysfunction. Patients on dialysis have a two- to five fold increase in coronary artery calcification compared to the general population and this is reflected in the high prevalence of CAD. However, the vascular calcification is a diffuse phenomenon in CKD and is associated with hyperphosphataemia. There is a suggestion that phosphate and ther unmeasured metabolites induce osteoblast-like activity in vascular smooth muscle. The resultant calcification means that vessels lose compliance and elasticity. Hence, there is an inability to adapt to changes in blood pressure, particularly hypotension. Vascular calcification is associated with adverse cardiovascular outcome and so may contribute to SCD. In the presence of one or both of autonomic dysfunction and rapid fluid shift associated with dialysis, it is clear why vascular calcification may cause circulatory collapse.Cardiac autonomic neuropathy may also contribute to arrhythmia. Both diabetes and uraemia are potential causes of autonomic neuropathy. Diabetic autonomic neuropathy is in part a vascular phenomenon, but at a microvascular level. Hyperglycaemia causes neuronal vasoconstriction and oxidative stress which results in nerve ischaemia. Diabetic autonomic neuropathy is associated with potential electrocardiographic markers of risk of SCD, such as heart rate variability. However, these alone are not proven to being dependent markers of riskCKD is also independently associated with endothelial dysfunction. Some pro-inflammatory cytokines and chemotactic factors are renally excreted but are not removed during dialysis.Hence, there is a state of chronic leucocyte activation. ‘Uraemia’ is a marker of a multitude of oxidative and pro-inflammatory metabolites that are not routinely measured but that are likely to contribute to this. Biochemical tests of inflammation such as C reactive protein are associated with adverse cardiovascular outcome in CKD. Chronic inflammatory processes may explain the increased mortality in patients who dialyse via centrally tunnelled venous catheters when compared to arteriovenous fistulae, which carry a much lower risk of infection.While poor left ventricular function is relatively common in the dialysis population, it is not prevalent enough to completely account for the high rate of SCD. Echocardiography studies in dialysis patients have shown that structural abnormalities are common. Dilated cardiomyopathy is seen in 36% of dialysis patients and left ventricular hypertrophy (LVH) in 74%.8 These are both associated with dialysis induced arrhythmia. The majority of haemodialysis patients will be hypertensive.The combination of this and volume

overload promotes LVH. Endomyocardial biopsies in dialysis patients with dilated cardiomyopathy show abnormal remodelling with interstitial fibrosis and myocyte hypertrophy. It is likely that these processes promote arrhythmias, as LVH is

associated with a 60% increased risk of SCD in diabetic dialysis patients.5 In addition, other pathological aspects of CKD, such as anaemia, uraemia, and hyperparathyroidism independently, contribute to myocardial fibrosis.

Haemodialysis is associated with dramatic changes in electrolytes with progressive changes between dialysis sessions and rapid changes during dialysis. The potential for arrhythmias associated with electrolyte changes and the chronic, oftenprofound electrolyte abnormalities associated with CKD are well established. Hyperkalaemia (table 2) is the most obvious of these, but hypokalaemia isvery common and associated with dietary restrictions, loop diuretics, and the low potassium content of dialysis fluid. The optimum pre-dialysis serum potassium concentration is 4.6e5.3 mmol/l, and using both too high and too low dialysatepotassium are associated with intra-dialytic arrhythmias.9 Both hyper- and hypokalaemia may precipitate life threatening arrhythmias.Hypocalcaemia occurs in most dialysis patients.The inability of the failing kidney to produce hydroxy-vitamin D results in poor dietaryabsorption of calcium. Arrhythmias rarely occur in the setting of hypocalcaemia alone as parasthesiae and muscular tetany will usually occur at a serum calcium level before cardiac risk is high, indicatingthe need for intervention.

SUPRAVENTRICULAR TACHYCARDIAS

The prevalence of atrial fibrillation (AF) in predialysis CKD patients is between 9-21%. This increases to between 13-27% in patients on long term haemodialysis. One in three dialysis patients will have experienced a supraventriculararrhythmia. This most commonly occurs in the hours immediately after dialysis and is associated with dialysis induced ischaemia and abnormal predialysispotassium. Ten percent to 15% will suffer AF independently of dialysis sessions. AF in these circumstances is associated with an 80% 5 year mortality. However, the arrhythmia itself is not an independent predictor of death, rather an indicatorof underlying cardiovascular disease. LVH and dilatation, coronary artery and valvular diseases are associated with AF in haemodialysis patients, andare all more common in these patients than the general population. Atrial flutter has been shown to occur as often in dialysis patients as AF. Hyperparathyroidismand LVH are more common in patients with either AF or flutter when comparedto other dialysis patients. The impact of atrial flutter on mortality in these patients is not known. Other tachycardias, such as atrioventricular re-entry (AVRT), atrioventricular nodal reentry (AVNRT), and atrial tachycardias are also lesswell reported in CKD and are not associated with dialysis. Antiarrhythmic drug treatment (ADT) is often approached with caution in ESRD because of thefear of adverse drug effects. However, dose adjustments are not often indicated . For example, there is no evidence that the adverse effects of b-blockade increase significantly with decline in GFR. While this indicates that maintenanceoses need not usually be changed for patients with CKD, it is vital to understand that the presence of CKD affects the transport and distribution of a drug as well as its metabolism.Therefore, signs of potential adverse effects of these drugs should be actively sought on a regular basis.The relative effectiveness of ADT in CKD is not well understood. Management should follow conventional therapy, with any necessary dose adjustments being made. Catheter ablation can be effective in this setting and is an appropriate strategy in difficult to manage patients, but willoccasionally be complicated by the vascular access difficulties commonly associated with the haemodialysis population. Another clinical challenge isthe use of anticoagulant therapy for AF in dialysis patients. There is an apparent excess of cerebrovascular events in anticoagulated dialysis patients,

but warfarin treatment in CKD stage 5 has never been prospectively studied. As with so many drugs used in CKD, the assumption of therapeutic benefitis extrapolated from studies which largely exclude dialysis patients. Its use should therefore be decided on an individual case basis. Figure 2 outlines the key points in the management of supraventricular tachycardia.

VENTRICULAR TACHYARRHYTHMIAS AND SCD

In the general population, the rate of SCD is 1event per 1000 patient years. In CKD, the risk increases by a hazard ratio of 1.1 for every 10 ml/min decline in GFR, with an overall event rate of up to 7.8 per 1000 patient years.12 This rate

increases 10-fold for patients starting dialysis and increases further with time on dialysis. United States Renal Data System (USRDS) data show an increase in SCD of 50% on Mondays and Tuesdays for haemodialysis patients. This reflects

the first dialysis activity after a 2 day weekend dialysis break.13 This may reflect repolarization instability from electrolyte change, poor homeostatic

adjustment, sudden fluid removal or an ischaemic effect of dialysis. However, a haemodialysis patient is most likely to die suddenly in the last12 h of the long weekend break between dialysis sessions, suggesting build up of fluid and electrolytes rather than their removal as the cause.Intra-dialytic cardiac arrest occurs at a rate of 7 per 100 000 dialysis sessions, with an equal occurrence of brady- and tachyarrhythmias. In comparison to peritoneal dialysis patients, haemodialysis\ patients are more likely to suffer SCD in the first 6 months after starting a dialysis programme. The rates merge for patients established on either modality for 6 months or more.This may reflect an early peak of sudden death in patients who are prone to arrhythmic death as a consequence of haemodialysis, or more simply that patients with multiple comorbidities areusually less able to self-care on peritoneal dialysis and therefore undertake haemodialysis.drug treatments almost universally exclude dialysis patients, and often patients with anything more than CKD stage 2 or 3. As a consequence there is no evidence based guidance on the medical management of arrhythmias in CKD. Minimising the risk of SCD in CKD patients currently focuses on general cardiovascular risk reduction. Tight control of blood pressure, fluid balance, serum phosphate, anaemia, and avoidance of hypo- and hyperkalaemia are all associated with cardiovascular survival benefit. Cardioselective and non-selective b-blockers

appear to be safe with no need for dose reduction.Although there have been no large randomized trials to this effect, b-blockade would seem to be advisable as a first line antihypertensive agent in advanced CKD and dialysis patients because of a definite reduction in cardiovascular mortality andan inferred reduction in the risk of SCD.15 This benefit may be due to the reduction in LVH and slower progression of heart failure associated withb-blocker use in these patients as much as a direct antiarrhythmic effect. The use of b-blockers does not increase the risk of hypotension compared to other antihypertensive agents.

Methodology

All data was collected from patients who admitted to CCU of al-Hussain teaching hospital. the patientsadmitted to the CCU do the research in the CCU, first we created a specific questionnaire which include a special data about the arrhythmia and its association to the CKD then the questionnaire was filled after asking the patients and this done by visiting the hospital twice to three time per day “once at morning , once at afternoon and once at night” for about 3 months.

Results

Figure 1: refer to the relationship between the arrhythmia and chronic kidney diseases,“0.0” no any type of arrhythmia” – AF” atrial fibrillation” – SVT “supraventricular tachycardia” – VT “ventricular tachycardia” – others”

address * TOA

TOA / Total
.00 / AF / SVT / others
address / Nasiriyah / 10 / 9 / 1 / 4 / 24
41.7% / 37.5% / 4.2% / 16.7% / 100.0%
Suq al-Shuyukh / 5 / 3 / 0 / 0 / 8
62.5% / 37.5% / 0.0% / 0.0% / 100.0%
Al-Shatra / 4 / 4 / 2 / 3 / 13
30.8% / 30.8% / 15.4% / 23.1% / 100.0%
Al Rifae / 1 / 0 / 0 / 0 / 1
100.0% / 0.0% / 0.0% / 0.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 7.365 / .713b

rural * TOA

Crosstab
TOA / Total
.00 / AF / SVT / others
rural / rural / 2 / 2 / 0 / 2 / 6
33.3% / 33.3% / 0.0% / 33.3% / 100.0%
urban / 18 / 14 / 3 / 5 / 40
45.0% / 35.0% / 7.5% / 12.5% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 1.979 / .631b

gender * TOA

Crosstab
TOA / Total
.00 / AF / SVT / others
male / 14 / 11 / 1 / 4 / 30
46.7% / 36.7% / 3.3% / 13.3% / 100.0%
female / 6 / 5 / 2 / 3 / 16
37.5% / 31.25% / 12.5% / 18.75% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 5.503 / .586b

smoking * TOA

Rosstab
TOA / Total
.00 / AF / SVT / others
Smoking / no smoking / 10 / 9 / 1 / 6 / 26
38.5% / 34.6% / 3.8% / 23.1% / 100.0%
smoking / 10 / 7 / 2 / 1 / 20
50.0% / 35.0% / 10.0% / 5.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 3.391 / .342b

duration * TOA

Crosstab
TOA / Total
.00 / AF / SVT / Others
duration / 11 / 9 / 1 / 6 / 27
40.7% / 33.3% / 3.7% / 22.2% / 100.0%
years / Count / 9 / 7 / 2 / 1 / 19
% within duration / 47.4% / 36.8% / 10.5% / 5.3% / 100.0%
Total / Count / 20 / 16 / 3 / 7 / 46
% within duration / 43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 3.022 / .396b

RF * TOA

Crosstab
TOA / Total
.00 / AF / SVT / Others
RF / no risk factor / 8 / 4 / 1 / 3 / 16
50.0% / 25.0% / 6.3% / 18.8% / 100.0%
one risk F / 6 / 4 / 0 / 0 / 10
60.0% / 40.0% / 0.0% / 0.0% / 100.0%
two RF / 5 / 6 / 2 / 2 / 15
33.3% / 40.0% / 13.3% / 13.3% / 100.0%
three RF / 1 / 2 / 0 / 1 / 4
25.0% / 50.0% / 0.0% / 25.0% / 100.0%
five RF / 0 / 0 / 0 / 1 / 1
0.0% / 0.0% / 0.0% / 100.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 11.035 / .562b

dialysis * TOA

Crosstab
TOA / Total
.00 / AF / SVT / Others
dialysis / off / 15 / 15 / 3 / 5 / 38
39.5% / 39.5% / 7.9% / 13.2% / 100.0%
on / 5 / 1 / 0 / 2 / 8
62.5% / 12.5% / 0.0% / 25.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 3.151 / .342b

sessions * TOA

Crosstab
TOA / Total
.00 / AF / SVT / others
sessions / no / 15 / 15 / 3 / 5 / 38
39.5% / 39.5% / 7.9% / 13.2% / 100.0%
once / 1 / 0 / 0 / 1 / 2
50.0% / 0.0% / 0.0% / 50.0% / 100.0%
twice / 3 / 0 / 0 / 1 / 4
75.0% / 0.0% / 0.0% / 25.0% / 100.0%
three times / 1 / 1 / 0 / 0 / 2
50.0% / 50.0% / 0.0% / 0.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 7.750 / .558b

Inv * TOA

Crosstab
TOA / Total
.00 / AF / SVT / others
Inv / normal Inv / 5 / 2 / 0 / 0 / 7
71.4% / 28.6% / 0.0% / 0.0% / 100.0%
one high reading / 5 / 1 / 1 / 1 / 8
62.5% / 12.5% / 12.5% / 12.5% / 100.0%
two high readings / 6 / 9 / 1 / 4 / 20
30.0% / 45.0% / 5.0% / 20.0% / 100.0%
three high readings / 3 / 3 / 1 / 2 / 9
33.3% / 33.3% / 11.1% / 22.2% / 100.0%
four abnormal readings / 1 / 1 / 0 / 0 / 2
50.0% / 50.0% / 0.0% / 0.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 9.247 / .702b

DRUGS*TOA

Crosstab
TOA / Total
.00 / AF / SVT / others
drugs / no drugs / 6 / 7 / 1 / 4 / 18
33.3% / 38.9% / 5.6% / 22.2% / 100.0%
one drug / 6 / 2 / 2 / 2 / 12
50.0% / 16.7% / 16.7% / 16.7% / 100.0%
two drug / 5 / 5 / 0 / 0 / 10
50.0% / 50.0% / 0.0% / 0.0% / 100.0%
three drugs / 1 / 0 / 0 / 1 / 2
50.0% / 0.0% / 0.0% / 50.0% / 100.0%
four drugs / 2 / 2 / 0 / 0 / 4
50.0% / 50.0% / 0.0% / 0.0% / 100.0%
Total / 20 / 16 / 3 / 7 / 46
43.5% / 34.8% / 6.5% / 15.2% / 100.0%
Fisher's Exact Test / 10.511 / .559b

CONCLUSION

The risk of arrhythmia associated with CKD is high and prevention through modification of cardiovascular risk factors should be of priority. atrial fibrillation was the commonest type of arrhythmia . there was high percent of patients with CKD were free from any type of arrhythmia ,supraventricular tachycardia was low in comparison with AF, while there was no evidence of ventricular tachycardia , and there was other type of arrhythmia in some patients .so the risk of ventricular arrhythmias appears to be significant.

DISCUSSION

The arrhythmia occurs more in male particularly AF while the SVT tends to occur more in the female . there is strong association between the smoking and all types of arrhythmia especially if the patient is smoker for many years.

Patients with other risk factors for developing arrhythmia like (hypertension, diabetes mellitus ,polycystic kidney ,stone , ..etc) tend to have the arrhythmia more than the risks free patients (the more the risks the higher the possibility to have arrhythmia ). The dialysis also has an impact on developing the arrhythmia.

We compared the result with another researches and the results are similar .

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