Cardiac Risk In ESRD Patient Dr.Badr Alhomayeed.md Nephrology and Kidney Transplant Consultant Feb/8/2014

Objectives: Relation ship between ESRD and cardiovascular morbidity and mortality. Risk factors for the development of cardiovascular disease in ESRD patient. Different cardiovascular manifestations in ESRD patient. Efforts to reduce cardiovascular risk in ESRD patient. Conclusion.

Cardiac Diseases in maintenance Hemodialysis patients: Result of the HEMO Study Kidney International (2004) 65,2380-2389

Causes of Death in Incident Dialysis Patients, 2009-2011, First 180 days USRDS 2013

Causes of Death in Prevalent Dialysis Patients, 2009-2011 USRDS 2013

Survival of Patients with Cardiovascular Diagnoses & Procedures, by Modality, 2009–2011 USRDS 2013

Risk Factors For Cardiovascular disease in ESRD patients. Henrich W L CJASN 2009;4:S106-S109

Congestive Heart Failure in Dialysis Patients Congestive heart failure is a common presenting symptoms of cardiovascular disease in dialysis population. CHF contributes significantly to mortality and morbidity and also worsens the quality of life in ESRD patients. Overt left ventricular hypertrophy (LVH) is very common. Myocardial disease can also reduce cardiac reserve, making the patient more vulnerable to episodes of hypotension during dialysis.

Rates of a CHF diagnosis in ESRD patients USRDS 2013

Heart failure in prevalent dialysis patients, by modality, 2011 USRDS 2013

Long-term Survival of Incident Hemodialysis Patients who are Hospitalized for Congestive Heart Failure, Pulmonary Edema, or Fluid Overload. Banerjee D et al. CJASN 2007;2:1186-1190

Salt+H2o retention , AVF, Anemia Hypertension Salt+H2o retention , AVF, Anemia LV pressure overload LV volume over load Eccentric LVH Vascular remodeling Conc. LVH Overload cardiomyopathy HPTH Malnutrition Uremic toxins Dialysis induced low BP LV dilatation & Hypertrophy Myocytes death Myocardial fibrosis Decrease capillary perfusion Diastolic dysfunction Systolic dysfunction Nephrol Dial Transplant (2000) 15 [Suppl 5]: 58–68

Cardiac fibrosis associated with increased mortality in ESRD patients. Henrich W L CJASN 2009;4:S106-S109

Reduction in systolic BP during hemodialysis in patients with and without HD-induced regional wall motion abnormalities (RWMAs). Burton J O et al. CJASN 2009;4:914-920

Change in EF at rest and during HD over 12 mo in patients with fixed reductions in segmental function of >60%. Burton J O et al. CJASN 2009;4:1925-1931

The association of hemodialysis-induced RWMAs with mortality and outcome. Burton J O et al. CJASN 2009;4:914-920

Unadjusted survival in patients with systolic and diastolic heart failure, by age, 2010–2011 Systolic Heart failure Diastolic Heart Failure USRDS 2013

Coronary artery disease in ESRD Approximately 20% of mortality in ESRD patient can be attributed to coronary artery disease. Many dialysis patients have more than one of the traditional risk factors , resulting in an even higher risk of adverse outcomes. Patients who have both DM and HTN have a 5-6 fold increased risk of having heart disease compared to those without history of either condition. Am J Kidney Dis.2005; 45(2):316

Biochemical, Functional, and Anatomic evaluation of Coronary Heart Disease in ESRD Stenvinkel P et al. JASN 2003;14:1927-1939

Stable Coronary Artery Disease Clinical manifestation: -Frequent hypotension or chest pain on hemodialysis. -Exercise induced chest discomfort. -Exertional dyspnea. -Sudden cardiac arrest. -Sudden cardiac death. -Arrhythmia.

Screening - If there is a change in symptoms related to IHD or clinical status (e.g. Recurrent low BP , CHF unresponsive to dry weight changes, or inability to achieve dry weight because of hypotension), evaluation for CAD is recommended. -Dialysis patients with significant reduction in LV systolic function (EF<40%) should be evaluated for CAD. - Evaluation for heart disease should occur at initiation of dialysis and include a baseline electrocardiogram (ECG) and echocardiogram. Both of these tests provide information pertinent to, but not restricted to, CAD evaluation. Annual ECGs are recommended after dialysis initiation. K/DOQI clinical practice guidlines

Screening - If the patient has “complete” coronary revascularization (i.e., all ischemic coronary vascular beds are bypassed), the first re-evaluation for CAD should be performed 3 years after coronary artery bypass (CAB) surgery, then every 12 months thereafter. - If the patient has “incomplete” coronary revascularization after CAB surgery (i.e., not all ischemic coronary beds are re vascularized), then evaluation for CAD should be performed annually. K/DOQI clinical practice guidlines

Screening - CAD evaluation should also include exercise or pharmacological stress echocardiographic or nuclear imaging tests. -“Automatic” CAD evaluation with stress imaging is currently not recommended for all dialysis patients . - Stress imaging is appropriate (at the discretion of the patient’s physician) in selected high-risk dialysis patients for risk stratification even in patients who are not renal transplant candidates. (C) -Patients who are candidates for coronary interventions and have stress tests that are positive for ischemia should be referred for consideration of angiographic assessment. (C) K/DOQI clinical practice guidelines

Acute Coronary Syndrome The evaluation and diagnosis of the dialysis patients with an acute coronary syndrome is based upon the constellation of symptoms and signs, findings on electrocardiogram, and levels of cardiac biomarkers. Dialysis patients with an acute coronary syndrome may present with atypical symptoms and signs.

Admission Variables for ESRD patient with ACS P.value Non Dialysis (n=534935) Dialysis (n=3049) Variable < 0.0001 Admission Diagnosis 229207 (43.8) 657 (21.8) MI 122752 (23.5) 713 (23.7) R/O MI 59943 (11.9) 291 (9.7) Unstable Angina 110836 (21.2) 1348 (44.8) other Systolic Blood Pressure 1.0000 143.8+/-32.3 143.6 +/- 39.3 Mean+/- SD 142 143 Median Diastolic Blood Pressure 80.7+/- 18.5 75.5+/-20.7 80 74 86.7+/-24.2 94.7+/- 24.1 Pulse BPM : Mean +/- SD 84 92 Pulse BMD: Median Herzog et al Circulation September 25, 2007

Admission Variables for ESRD patient with ACS P.value Non dialysis (n=534935) Dialysis (n=3049) Variables < 0.0001 3553442 (68.3) 1325 (44.4) Chest Pain 394914 (75.2) 1775 (58.4) No CHF 83433 (15.9) 764 (24.1) Rales, JVP distention 40074 (7.6) 461 (15.2) pulmonary oedema 6778 (1.3) 39 (1.3) Cardiogenic Shock ECG: 188099 (35.9) 579 (19.1) ST elevation 1.0000 151492 (28.9) 840 (27.7) ST depression 187650 (35.8) 1338 (44.1) Non specific 46744 (8.9) 970 (5.6) Q wave 30134 (5.8) 244 (8.1) LBBB 30485 (5.8) 198 (6.5) RBBB 0.3294 40196 (7.7) 193 (6.4) Normal 92146 (17.6) 760 (24.1) Other Herzog et al Circulation September 25, 2007

Admission Variables for ESRD patient with ACS P.values Non dialysis (n=534935) Dialysis (n=3049) Variables Myocardial Infarction type < 0.0001 126566 (23.7) 508 (16.7) Antero/septal 163559 (30.6) 555 (18.2) Inferior 23060 (4.3) 65 (2.1) Posterior 66367 (12.4) 293 (9.6) Lateral 1.0000 3624 (0.7) 13 (0.4) Rt. Ventricle involvement 229312 ( 42.9) 1892 (62.1) Unspecified/other 199602 ( 37.4) 78 (22.1) Q wave 334793 (62.6) 2371 ( 77.8) Non Q wave Herzog et al Circulation September 25, 2007

Rates of an AMI event in ESRD patients USRDS 2013

Estimated mortality of dialysis patients after acute myocardial infarction (MI). Herzog C A JASN 2003;14:2556-2572

Cause Specific Mortality of Dialysis patients after Coronary Revascularization Herzog C A et al. Nephrol. Dial. Transplant. 2008;23:2629-2633

Sudden Cardiac Death In ESRD Sudden Cardiac Death (SCD) is the single most common cause of death in dialysis patients. It accounts for 20-30% of all deaths. Over all incidence of SCD in this population is greater than coronary events. The risk of SCD persist after coronary revascularization.

Rate of Sudden Cardiac Death in Prevalent ESRD patient by Modality USRDS 2013

Distribution of deaths according to day of the week for hemodialysis patients Bleyer et al, kidney International 1999.55:1553-1559

Probability of Sudden Cardiac Death in Incident ESRD patient by modality USRDS 2103

Risk Factors for Sudden Cardiac Death among ESRD Dialysis Patient Herzog et al. Seminars in Dialysis, 2008

Prevention of sudden death in dialysis patients. Reduction of  ‐ Cardiac hypertrophy &  fibrosis ‐ Fatal arrhythmia ‐ Heart rate variability Avoiding low K  dialysate & rapid   electrolyte shifts: To avoid: ‐ QT dispersion   ‐ Réentrant arrhythmias   ‐ Premature VES Beta blockers Prevention  of  sudden  death ACEI and ARBs Reduction of   ‐ Cardiac hypertrophy & fibrosis       ‐ Antifibrillary activity ‐ Ventricular arrhythmia ‐ Heart rate variability   ‐ Increase in baroreflex      sensitivity ‐ Reduced risk of acute MI To avoid ‐ Cardiac arrest and      ‐ Life‐threatening ventricular tachycardia External &  implantable defibrillator Blood Purif 2010;30:135–145

Atrial Fibrillation End stage renal disease patients are more at risk for atrial fibrillation than the general population. AF is more prevalent in end-stage renal disease patients compared to age-matched individuals with normal renal function . Hemodialysis is associated with higher risk for AF compared to peritoneal dialysis. Left ventricular hypertrophy and electrolyte shift are strong predisposing factors for development of AF.

Incidence of Atrial Fibrillation in Patient with ESRD Zimmerman D et al. Nephrol. Dial. Transplant. 2012;27:3816-3822

Prevalence of Atrial Fibrillation in Patient with ESRD Zimmerman D et al. Nephrol. Dial. Transplant. 2012;27:3816-3822

Mortality in patients with ESRD with and without atrial fibrillation. Zimmerman D et al. Nephrol. Dial. Transplant. 2012;27:3816-3822

Anticoagulation Bleeding Thrombosis

Stroke in patients with ESRD with and without atrial fibrillation. Zimmerman D et al. Nephrol. Dial. Transplant. 2012;27:3816-3822

Valvular Heart disease Valvular heart disease is common in patients on maintenance dialysis. Valvular and annular thickening and calcification of the heart valves with subsequent development of regurgitation and/or stenosis of the affected one. Aortic and mitral valve are commonly affected.

Predisposing Factors: 8-Infective endocarditis 1-Secondary hyperparathyrodisim 9-Mitral valve prolapse 2-HTN 10-High cardiac out put state 3-DM 11-Anemia 4-LVH 12-Arteriovenous fistula 5-Malnutrition/ inflammatory complex 13-Hyperlipidemia 6-Uremia 7-Hypertrophic cardiomyopathy

Pericardial disease Patients with end-stage renal disease may develop pericarditis and pericardial effusions, and less commonly, chronic constrictive pericarditis. Two forms of pericarditis in renal failure have been described including uremic and dialysis-associated. Uremic pericarditis results from inflammation of the visceral and parietal membranes of the pericardial sac. At least two factors may contribute to dialysis associated pericarditis: inadequate dialysis and/or fluid overload . Alpert et al Am J Med Sci. 2003;325(4):228

Conclusion: End stage renal disease is a situation with a cardiovascular risk profile of almost unique severity. ESRD patient is at high cardiac risk precipitated by both traditional and non traditional risk factors. Different cardiac manifestations with various degree of severity and presentations are unique to ESRD patient on dialysis. Sudden cardiac death is the single most common cause of death in ESRD patient.