On Referral to our Unit

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2 Case Presentation By Samah Ibrahim Abdel Meguid Idris, MD Internal Medicine & Nephrology Consultant Head of Hemodialysis Unit Ahmed Maher Hospital, Alexandria

3 Patient Data MEA 27-year-old male patient From Alexandria Single Started hemodialysis since 10 years ago Cause of renal failure was unknown as he was referred to our unit in December 2012 Complaining of worsening exertional dyspnea and chest tightness

4 On Referral to our Unit The patient was suffering from severe hypertension (average readings 180/110) Fixed flexion deformity of the left elbow and wrist Persistent chest tightness during dialysis sessions Serial lab investigations were done ECG and Echo revealed ischemic changes, moderate left ventricular hypertrophy (LVH), mild-to-moderate calcific aortic stenosis (AS)

5 Patient s Previous Investigations Hb. (g/dl) /7.4/ /8.2 T-sat (%) /35 38/22 Ferritin >1000/ Albumin (mg/dl) Calcium (mg/dl) Phos. (mg/dl) /10.2/ /2.8/ PTH / / /

6 Patient s Drug History For hypertension: Alpha-methyl DOPA, Bisoprolol & Amlodipine For Calcium/Phosphate: 1-alpha Vitamin D, Sevelamer, Aluminum hydroxide & Cincalcet For anemia: Repeated blood transfusions, recombinant erythropoietin & intravenous iron infusions

7 Patient s Last Investigations Hemoglobin: 8.1 g/dl Pre-dialysis creatinine: 7 mg/dl Post-dialysis creatinine: 5.4 mg/dl Iron profile: Albumin 3.2 mg/dl, Iron 44, Ferritin 814, TIBC 200, T-sat 22% PTH: 950 pg/ml

8 The patient was referred for follow-up echocardiography which revealed

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15 Echocardiography Conclusions Dilated LV dimensions with preserved global systolic function Severe concentric LVH Moderate LV diastolic dysfunction Moderate calcific AS Mild MR & dilated LA Dilated RA & good RV systolic function Minimal TR & high probability of Pulmonary Hypertension

16 Dialysis patients are at risk for developing AS, and tissue calcification as hyperphosphataemia, hypercalcaemia, and hyperparathyroidism combine to predispose patients to the development and progression of calcification Urena P, Malergue MC, et al. Evolutive aortic stenosis in hemodialysis patients: analysis of risk factors. Nephrologie 20: , 1999

17 The aortic valve is submitted to turbulent blood flow and pressure gradients from the rapid flow of blood through the valve This repeated shear stress can lead to fibrosis and calcification which further disturbs blood flow and increases its velocity across the valve, creating a vicious cycle

18 In ESRD patients treated with hemodialysis, fluid overload, anemia and shunts across arterio-venous fistulae can all cause a state of high cardiac output, which lead to increased flow velocity and turbulence across the aortic valve and predispose to fibrosis and calcification, and ultimately obstructive valvular stenosis. Patients on dialysis also have higher resting heart rates; more frequent opening and closing of the valve causes more mechanical shear stress over time.

19 As the degree of AS progresses, the left ventricle is subjected to pressure-overload leading to compensatory hypertrophy of the ventricle. This mechanism is initially adaptive, preserving normal left ventricular systolic function. With time, however, this becomes a maladaptive process and causes impaired relaxation and abnormal diastolic filling of the left ventricle. Ultimately, sustained pressure overload may lead to dilatation of the left ventricle and impaired systolic function.

20 Challenges in Clinical Presentation The principal symptomatic manifestations of AS are: Dyspnea Chest pain Syncope Anginal chest pain may reflect functional ischemia caused by increased myocardial oxygen demand and impaired supply, or may be attributable to concomitant coronary artery disease.

21 The interpretation of these symptoms is challenging in those patients Dyspnea is reported in up to 50% of dialysis patients, and has many potential causes: fluid overload, anemia, pulmonary hypertension, bacteremia, valvular lesions, or acute coronary syndromes

22 Challenges in Assessment The key investigation for patients with suspected or proven AS is echocardiography, permitting direct visualization of the valve which may appear thickened with visible calcification and reduced movement. Rapid progression in AS is associated with a worse prognosis and underscores the importance of regular assessments to ensure timely intervention on the valve.

23 Echocardiographic measurements should be made at consistent timings relative to dialysis. It may be possible to minimize the likelihood of a variable cardiac output state affecting the calculated valve area by always performing the echocardiogram on a day when the patient is not dialyzing.

24 If the degree of valve calcification and cusp mobility indicates the aortic valve is severely stenosed, then the possibility of low-flow, low-gradient severe AS should be considered. A careful assessment of the left ventricular systolic function will be valuable. Dobutamine stress echocardiography may also help clarify the severity of the aortic stenosis by augmenting cardiac output and transvalvular flow. Invasive cardiac catheterization can contribute to the assessment of a patient with aortic stenosis.

25 Challenges in Management 1-The Assessment of a Dialysis Patient with AS: The evaluation of a patient with AS hinges on their symptomatic status Many dialysis patients also suffer from fatigue and muscle weakness and so reduce their activity levels, though symptoms or hypotension on dialysis may provide a clue to a hemodynamically significant lesion

26 2-Decision of correct timing and type of intervention: The clinician must synthesize all available information including the extent of calcification, the severity of obstruction, the left ventricular function, the ability to tolerate hemodialysis sessions, the need for any other surgery (CABG with valve replacement)

27 3- Intradialytic Problems: Patients with hemodynamically significant AS are vulnerable to episodes of profound hypotension on dialysis The most common dialysis-induced arrhythmia is atrial fibrillation. Its occurrence in patients with hemodynamically significant aortic stenosis can precipitate dramatic hypotension and circulatory collapse Controlled ultrafiltration & meticulous assessment of fluid status with documentation of dry weight may help mitigate some of these potential intradialytic complications

28 4- Risk of Endocarditis: The incidence of infective endocarditis is 3% in the general population on long-term dialysis This risk is increased in patients with underlying valvular lesions, and especially in those with infected vascular access sites. Arteriovenous fistulas may pose as significant a risk of endocarditis as indwelling catheters Over half of dialysis patients diagnosed with infective endocarditis have abnormal valves, and the aortic valve is involved 40% of them

29 Treatment General and Specific for Dialysis Patients Calcification of the aortic valve, once apparent, is irreversible. Prevention of calcification may perhaps be attained by reducing calcium intake and controlling hyperphosphataemia and hyperparathyroidism. Patients with indwelling catheters and fistulae are at increased for endocarditis, and appropriate antibiotic prophylaxis must be considered in certain clinical circumstances. Fluid overload and high cardiac output states (such as those caused by anemia or high flow fistulae) are problematic as these may accelerate the progression of degenerative valvular calcification.

30 Ultrafiltration during dialysis sessions must not excessively drop the diastolic filling pressures, as the hypertrophied ventricle of aortic stenosis is poorly compliant and may not tolerate the fall in filling pressures; hypotension readily occurs. The more rapid vascular refilling accompanying a fluid overloaded state lessens the risk of this hypotension but at the obvious cost and risk of extracellular fluid (ECF) expansion. Extending dialysis time or a stronger emphasis on sodium restriction are better solutions to address the predisposition to intradialytic hypotension (IDH).

31 Surveillance echocardiography may be warranted at more frequent than usual intervals in dialysis patients, due to the often rapid progression in the degree of stenosis The gold standard treatment remains surgical aortic valve replacement. Younger patients should be considered for mechanical valves providing they are not at an unacceptably elevated risk for bleeding or thrombotic complications The aim of treatment is to prevent sudden cardiac death or irreversible left ventricular systolic dysfunction

32 Ahmad, Y., Bellamy, M. F. and Baker, C. S. R. (2017), Aortic Stenosis in Dialysis Patients. Semin Dial. doi: /sdi First published: 26 February 2017

33 Thank you for your Attention

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