Cardiac status in patients of chronic kidney disease : an assessment by non-invasive tools

Background: Chronic Renal Insufficiency is a major public health problem. Cardiovascular Disease is the leading cause of morbidity and mortality in patients at every stage of Chronic Kidney Disease. There is a 10-200 fold increased risk of cardiovascular disease in those with Chronic Kidney Disease compared to the age and sex matched with general population, depending on the stage of Chronic Kidney Disease. Objective: The objective of the study was to see correlation, if any, of cardiac status and stage of kidney disease. Materials and methods: The study was conducted at M. M. Institute of Medical Sciences and Research, Mullana, Ambala. Thirty patients of Chronic Kidney Disease were included in the study. Chronic Kidney Disease is defined as kidney damage lasting for more than 3 months characterised by structural or functional abnormalities of the kidney, with or without decreased Glomerular Filtration Rate (GFR), according to the K/DOQI Guidelines. Inclusion criteria were based on symptomatology and clinical history of features suggestive of Chronic Kidney Disease. Symptoms, Signs and history of the patients were used to filter out patients who did not fit in the criteria and selected patients on the basis of criteria were further evaluated and investigated. All patients were subjected to detailed history and clinical examination. Patients with age <20 years, with history of Diabetes Mellitus, Dyslipidemia, Intrinsic Diseases of Ventricles, Congenital Heart Disease and chronic smokers were excluded from the study. A standard 12 lead ECG was done in all cases. Echocardiography was done in ECHO lab of Cardiology unit in MMIMSR. Echocardiographic assessment was done by using Model vivid Colour Doppler Echocardiography machine of GE make. Apical four chamber view was employed to obtain the measurements of Left ventricular volume in diastole and systole, Ejection fraction; Left Ventricular Indices were assessed and then were used to calculate Left Ventricular Mass by using the cube formula proposed by Devereux. Patients included in the study were treated as per the standard treatment schedule. The data obtained was analysed with appropriate statistical analysis tools at the end of the study and conclusive evidence was derived. Results: In the present study the mean Left Ventricular Mass was 249.76 ± 69.35 gms with 73% study cases having Left Ventricular Mass more than the reference range, also Left Ventricular Mass showed a progressive rise with increase in S. Creatinine levels. In the present study, Left Ventricular dysfunction was seen in nearly half of the cases while approximately one-fourth cases (23%) also had Systolic Dysfunction. Pericardial Effusion was also observed in 10 % the study cases in the present study. Conclusion: Cardiac functions particularly Left Ventricular parameters. Left Ventricular free wall thickness and Left Ventricular Mass being common abnormality in CKD patients.


Introduction:
Chronic Renal Insufficiency is a major public health problem.The number of patients with End Stage Renal Disease has steadily increased over the years.In the United States, the rate has been reported as 6-7% per year 3 In India, the incidence of Chronic Kidney Disease was suggested to be 100 per million populations by single centre studies from tertiary care hospital.Upto 0.8% of the population may suffer from Chronic Kidney Disease thereby putting the number at about 7.85 million of the 1billion population 4 .Effect of chronic kidney disease on cardiovascular system Cardiovascular Disease is the leading cause of morbidity and mortality in patients at every stage of Chronic Kidney Disease.There is a 10-200 fold increased risk of cardiovascular disease in those with Chronic Kidney Disease compared to the age and sex matched with general population, depending on the stage of Chronic Kidney Disease.Between 30-45% patients of Chronic Kidney Disease reaching stage 5 Chronic Kidney Disease already have advanced cardiovascular complications, so many patients succumb to cardiovascular disease before ever reaching stage 5 Chronic Kidney Disease 12 .

Ischemic vascular changes
The presence of any stage of Chronic Kidney Disease is a major risk factor for ischemic cardiovascular disease, including occlusive coronary, cerebrovascular and peripheral vascular disease.The increased prevalence is due to traditional (classic) i.e.Hypertension, Hypervolemia, Dyslipidemia, Sympathetic overactivity and hyperhomocysteinemia and non traditional (CKD related) risk factors like Anemia, Hyperphosphatemia, Hyperparathyroidism, Sleep Apnoea, and generalised inflammation.Coronary reserve, defined as increase in coronary blood flow in response to greater demand is also attenuated.Cardiac Troponin levels are also elevated in Chronic Kidney Disease without evidence of acute ischemia, thus complicating the diagnosis of myocardial infarction in these patients 7 .

Peripheral vascular disease
The inflammatory state associated with reduction in kidney function is reflected in increased circulating acute phase reactants, such as inflammatory cytokines and C-reactive protein, with corresponding fall in the negative acute phase reactants such as albumin and fetuin.The inflammatory state accelerates vascular occlusive diseases, and low level of fetuin permits more rapid vascular calcification, especially in the face of hyperphosphatemia.

Heart failure
In Chronic Kidney Disease, abnormal cardiac function secondary to myocardial ischemia, left ventricular hypertrophy, and frank cardiomyopathy, along with salt and water retention often results in heart failure or even episodes of pulmonary edema.A form of low pressure pulmonary edema can also occur in advanced Chronic Kidney Disease, manifesting as shortness of breath and bat wing distribution of alveolar edema fluid on the chest x-ray.This occurs due to increased permeability of alveolar capillary membranes due to uremic state.Other Chronic Kidney Disease-related risk factors, including anaemia and sleep apnoea, may also contribute to risk of heart failure 6 .Hypertension and left ventricular hypertrophy LVH is highly prevalent in both stages 3 and 4 CKD and dialysis patients and represents a physiologic adaptation to a long term increase in myocardial work requirements 8 .Cardiomyopathy are among the strongest risk factors for cardiovascular morbidity and mortality in patients with Chronic Kidney Disease and, are thought to be related primarily, but not exclusively, to prolonged hypertension and ECFV overload.Also anaemia due to Chronic Kidney Disease can also generate high cardiac output state and subsequent heart failure 11 .

Pericardial Disease
Chest pain with respiratory accentuation, accompanied by a friction rub, is diagnostic of pericarditis.Classic electrocardiographic abnormalities include PR-interval depression and diffuse ST-segment elevation.Pericarditis can be accompanied by pericardial effusion that is seen on echocardiography and can rarely lead to tamponade, however, the pericardial effusion can be asymptomatic, and pericarditis can be seen without significant effusion.Pericarditis is seen in advanced uraemia, and is more often observed in underdialyzed, nonadherent patients than those in those starting and those adherents to dialysis.Pericarditis is frequently seen in peritoneal dialysis patient than it occurs in haemodialysis patient 10 .Arrhythmias Arrhythmias are very frequently seen in elderly during dialysis because of metastatic complication, amyloidal infiltration, coronary heart disease, cardiac hypertrophy, and hypertension are more frequent than in younger patients.Uraemia, hyperkalemia, acidosis and disorders of calciumphosphate balance have been associated with higher rates of supraventricular and ventricular arrhythmias.Due to presence of conditions like left ventricular hypertrophy, left ventricular dilation, heart failure and valvular diseases, higher rates of almost all arrhythmias are seen in Chronic Kidney Disease, including bradyarrythmias and heart block 12 .

Objective:
The objective of the study was to see Correlation, if any, of cardiac status and stage of kidney disease.

Materials and methods:
The study was conducted at M. M. Institute of Medical Sciences and Research, Mullana, Ambala.Thirty patients of Chronic Kidney Disease were included in the study.The patients taken from Outpatient department (OPD) and Indoor wards of the department of Medicine and Emergency Department.Chronic Kidney Disease is defined as kidney damage lasting for more than 3 months characterised by structural or functional abnormalities of the kidney, with or without decreased Glomerular Filtration Rate (GFR), according to the K/DOQI Guidelines1.

Inclusion criteria
Inclusion criteria was based on symptomatology and clinical history of features suggestive of Chronic Kidney Disease.Symptoms, Signs and history of the patients were used to filter out patients who did not fit in the criteria and selected patients on the basis of criteria were further evaluated and investigated.All patients were subjected to detailed history and clinical examination All patients were subjected to following investigations at the beginning of the study, like - History: a detailed history regarding duration of illness, any treatment received and past history of illness was taken.Age and sex of the patient was noted.b.
General Physical Examination: a detailed general physical examination was done with special reference to pulse rate and character, blood pressure, jugular venous pressure, presence of pallor, clubbing or pedal edema.c.
Respiratory and Cardiovascular Examination: a thorough examination of chest and CVS was done with emphasis of features of emphysema and evidence of left ventricular overload i.e. shortness of breath, pulmonary edema, orthopnoea and paroxysmal nocturnal dyspnoea, soft first heart sound, apex beat displaced outwards, heave often present, high pitched pansystolic murmur at the apex, radiating to the back or clavicular area etc.

2.
Chest Roentgenogram Posteroanterior films were obtained in all subjects.The following parameters were noted: -Low, flat or irregular diaphragm -Air trapping or bullae -Increased transradiancy -Main pulmonary artery shadow enlargement -Prominent bronchovascular markings -Cardiomegaly/ narrow heart shadow -Increased distance between intercostal spaces -Pleural Effusion -unilateral/ bilateral.

Electrocardiography (ECG)
A standard 12 lead ECG was done in all cases.Abnormalities on the ECG often provide the first evidence of cardiac dysfunction in patients in whom it is suspected.Diagnosis of LVH on electrocardiogram was made using Romhilt-Estes point score system95.Patients included in the study were treated as per the standard treatment schedule.The data obtained was analyzed with appropriate statistical analysis tools at the end of the study and conclusive evidence was derived.The study was ethically approved by ethical committee of M.M.Insttitute of Medical Sciences & Resarch, Mullana (Ambala), India.

Observations:
The study was conducted at M.M. Institute of Medical Science and Research, Mullana, Ambala.Thirty patients of Chronic Kidney Disease satisfying the Inclusion criteria were taken from Outpatients department, Indoor wards of department of Medicine and Emergency department.These patients were then subjected to Clinical examination and routine investigations along with some special investigations like Echocardiography.The observations hence made have been tabulated and presented as follows.In the present study, Hemoglobin levels were below 10 gm/dl in all the patients (except 1).More than one-third of the patients had Hemoglobin levels below 7gm/dl, thereby emphasising the need for correction of Anemia in patients of CKD.This was comparable with the study by Foley et al 17 having mean Hemoglobin levels of 8.4 ± 1.7 gm/dl in CKD patients and 5.45 ± 2.26 gm/ dl in a study by London GM 25 .
In present study, mean S. Potassium levels in CKD patients 5.54 ± 0.54 mEq/ L. This was comparable to S. Potassium levels of ≥ 5 mEq/ L in studies conducted by Singh NP et al 25 and Hayes et al 20 .
If LVHis detected on ECG it usually means that an advanced degree of cardiac involvement has already occurred.ECG is inexpensive, easy to perform and provides additional prognostic information.In this study the Romhilt-Estes Point score system 27 was used to find the prevalence of LVH in CKD patients.Subjects having a score of 5 or more points were considered to have LVH in Hypertensive subjects.
In the present study all the cases had ECG changes, with LVH present unanimously in all the ECGs.In almost 1/4th of the patients (23%) it had changes associated with Hyperkalemia viz-Tall tented Twaves, prolonged QT interval.The ECG changes were in confirmity with those in study conducted by Stewart GA et al 9 , who observed > 80% had LVH, also prolonged QT interval was found associated with poor Renal function, these features were also comparable to another study by Makusidi et al 19

4 .
Echocardiography Echocardiography was done in ECHO lab of Cardiology unit in MMIMSR.Echocardiographic assessment was done by using Model vivid Colour Doppler Echocardiography machine of GE make.Patients were examined in the left lateral and supine position in quiet respiration.a. M Mode Echocardiography Left ventricular dimensions were obtained by directing the ultrasonic beam at the chamber between the mitral valve echoes and papillary muscle echoes in the left parasternal long axis view.Following measurements were made:--Left ventricular internal diameter in diastole and systole -Interventricular septum thickness in diastole and systole b.Two Dimensional Echocardiography Apical four chamber view was employed to obtain the measurements of Left ventricular volume in diastole and systole , Ejection fraction, Left Ventricular Indices were assessed and then were used to calculate Left Ventricular Mass by using the cube formula proposed by Devereux 31 .LV Mass = Myocardial Volume x 1.05 g/cm3 = [(IVSd + LVIDd + LVPWd)]3 -(LVIDd)3 x 1.05 g/cm3.

Table 1 :
Showing age and gender distribution of patient's age (in years)

Table 2 :
Showing duration since diagnosis in patients of CKD duration since diagnosis

Table 3 :
Creatinine value was more than 6mg/dl in most of the study patients -93.3%.
showing s.Creatinine levels in CKD Patients s.creatinine (mg/dl)

Table 4 :
showing ECG findings in patients with CKD ECG abnormalities were present in all cases.Left Ventricular Hypertrophy present in 100% study subjects; while in 23.3% patients LVH was associated with changes suggestive of Dyselectrolytemia (Hyperkalemia).ECG abnormalities were present in all cases.Left Ventricular Hypertrophy present in 100% study subjects; while in 23.3% patients LVH was associated with changes suggestive of Dyselectrolytemia (Hyperkalemia).The Thickness of IVSd and LVPWd were higher than normal but it was the Left Ventricular Mass which was significantly increased confirming Left ventricular Hypertrophy.However the Systolic and diastolic functions of Left ventricle were normal.

Table 5 :
Showing mean values of various echo Pericardial Effusion was also observed in 10 % the study cases in the present study.The prevalence of Pericardial Effusion in CKD patients similar with study byKleiman JHet al 21 who observed Uremic Pericardial Effusion in 6% among their study cases who had pericardial effusion more than 100ml and concluded CKD as one of the cause of Pericardial Effusion.Conclusion: Chronic Kidney Disease is a fairly common disease with almost comparable preponderance in either of the sexes.Etiology being multifactorial, fairly good proportion of CKD patients has etiology like Chronic Glomerulonephritis, Autosomal Dominant Polycystic Kidney Disease, other than common etiology of Hypertension and Diabetes Mellitus.Kidney and Heart have curious relationship.Kidney is one organ which many be the cause of hypertension and it is also the organ which suffers most with the effects of hypertension.Hypertension is one of the leading disease causing increased cardiac morbidity and mortality.The disturbed Renin-Angiotensin System in CKD largely affects the cardiac physiology.Cardiac functions particularly Left Ventricular parameters.Left Ventricular free wall thickness and Left Ventricular Mass being common abnormality in CKD patients.Increase in severity of the disease with increasing levels of S. Creatinine and changes in Left Heart geometry as assessed on echocardiographic examination have a direct correlation.ECG is quick, cheap and readily available investigation to document Left Ventricular Hypertrophy but Echocardiography is a better option.Echocardiography is a sensitive, non-invasive and affordable modality to assess cardiac functions in Chronic Kidney Disease patients.Electrocardiogram and Chest radiography are good tools to document changes in anatomy and effects on coronary circulation, but Echocardiogram remains an excellent tool for functional assessment which takes the main stay of therapeutic decision and prognostic assessments and should be used regularly in all patients of CKD for early detection of cardiac dysfunction.