Cardiovascular Complications of CKD

Abstract

Cardiovascular complications in CKD patients are common and cause increased morbidity and mortality. The mechanisms of cardiac and vascular changes are often kidney specific and hence risk factors are non-traditional and traditional. The management of cardiovascular disease in CKD can be challenging due to side effects of commonly used therapy and the lack of evidence in advanced CKD patients. This chapter discusses the diagnosis and management of coronary artery disease, acute coronary syndromes, heart failure, cardiac arrythmias and valvular diseases in patients with chronic kidney disease.

Questions

• 1. A 65-year-old male with CKD stage G3aA2 is seen for the first time in the general nephrology clinic, having been referred by his primary care physician. He is known to have hypertension, for which he takes Ramipril 5 mg orally once daily. He reports several episodes of chest pain over the past year, all of which have occurred at a high level of exertion. There have been no episodes occurring at rest and he is pain free at present. An ECG performed in clinic meets voltage criteria for left ventricular hypertrophy, there are no acute indicators of ischaemia. You send blood tests and request an echocardiogram. What would be the most appropriate next line investigation?

  • A. Invasive coronary angiography

  • B. Coronary artery calcium score

  • C. Exercise ECG

  • D. Dobutamine stress echocardiogram

  • E. Cardiac MRI

  Answer: D. Dobutamine stress echocardiogram.

  • A. Incorrect: Invasive coronary angiography—Given the fact that his pain is produced at high levels of exertion, the risks associated with invasive coronary angiography this would not be the first line investigation of choice. If, however, he was suffering from angina symptoms at a very low level of exertion or at rest then moving straight to invasive angiography may be appropriate.

  • B. Incorrect: Coronary artery calcium score—A hypertensive 65-year-old male with CKD is very likely to have a raised coronary artery calcium score, this result would not give any further information on likely territories involved and would therefore be of limited diagnostic utility

  • C. Incorrect: Exercise ECG—An exercise ECG would be difficult to interpret due to his underlying left ventricular hypertrophy.

  • D. Correct: Dobutamine stress echocardiogram—A functional test is the test of choice for assessing coronary artery disease in patients with CKD. The presence of regional systolic dysfunction on stress testing would suggest the presence of coronary artery disease.

  • E. Incorrect: Cardiac MRI—While cardiac MRI may give some indication of underlying ischaemic damage or myocardial scarring it would not be a first line test for assessing the presence of coronary artery disease.

• 2. A 51-year-old gentleman with no significant past medical history is newly diagnosed with G3aA2 CKD. His eGFR is 50 mL/min/1.73 m². A lipid profile is as follows: LDL cholesterol 3.5 mmol/L, HDL cholesterol 0.70 mmol/L, triglycerides 2.20 mmol/L.

  What is the most appropriate management?

  • A. Statin in combination with ezetimibe

  • B. Fenofibrate

  • C. Lifestyle advice

  • D. Ezetimibe monotherapy

  • E. Statin in combination with fenofibrate

  Answer: A. Statin in combination with ezetimibe.

  • A. Correct: Statin in combination with ezetimibe—the non-dialysis population, patients over the age of 50 years with an eGFR of less than 60 mL/min/1.73 m² should receive statin and ezetimibe.

  • B. Incorrect: Fenofibrate—Fibric acid derivatives have been considered in relation to managing hypertriglyceridemia—both in terms of reducing cardiovascular risk and preventing pancreatitis. However, there is insufficient evidence of any clinical benefit and they are not recommended.

  • C. Incorrect: Lifestyle advice—Lifestyle measures typically only reduce serum cholesterol by a small margin and therefore pharmacological measures are necessary. Nonetheless, lifestyle advice should be provided in tandem given the positive impact on general health (independent of effect on lipid levels).

  • D. Incorrect: Ezetimibe monotherapy—Although ezetimibe has lipid lowering properties, only regimens which include a statin have been shown to reduce adverse cardiovascular events in patients with CKD.

  • E. Incorrect: Statin in combination with fenofibrate—The patient is over 50 years of age and given that he has an eGFR of <60 the KDIGO lipid guidelines recommend treatment with a statin or combination therapy with a statin and ezetimibe.

• 3. Which of the following statements is true regarding the clinical presentation of ischaemic heart disease amongst the CKD population?

  • A. STEMI is more common than NSTEMI.

  • B. The CKD patient presenting with an acute coronary syndrome will most commonly report central crushing chest pain radiating to the left arm.

  • C. Patients tend to present with less obvious chest pain and more prominent heart failure.

  • D. Patients are more present with exertional angina than an acute MI.

  • E. Dyspnoea is unlikely to be associated with acute MI.

  Answer: C. Patients tend to present with less obvious chest pain and more prominent heart failure.

  • A. STEMI is more common than NSTEMI: Incorrect—NSTEMI presentations are more common than STEMI in the CKD population.

  • B. The CKD patient presenting with an acute coronary syndrome will most commonly report central crushing chest pain radiating to the left arm: Incorrect—while of course patients may present with “classical” ischaemic chest pain, atypical presentations with dyspnoea and heart failure are more common.

  • C. Patients tend to present with less obvious chest pain and more prominent heart failure: Correct—Presentations of acute coronary syndromes in the CKD population are atypical, with heart failure symptoms being more obvious than chest pain.

  • D. Patients are more likely to present with exertional angina than an acute MI: Incorrect—The opposite in fact is true, patients are more likely to present with an MI than stable exertional angina.

  • E. Dyspnoea is unlikely to be associated with acute MI: Incorrect—As discussed above, ACS presentations in the CKD patient are atypical and heart failure symptoms such as dyspnoea are prominent.

• 4. A 79-year-old woman with a past medical history of type 2 diabetes mellitus, hypertension and G3bA2 CKD presents to the emergency department with central chest pain and breathlessness. An ECG demonstrates 2 mm ST segment depression in the lateral chest leads. Blood results reveal the following: Urea 14.2 mmol/L, Creatinine 148 mmol/L, eGFR 36 mL/min/1.73 m². Her initial troponin is 72 ng/L rising to 280 ng/L at 3 h. She is diagnosed with a non-ST elevation MI and loaded with dual antiplatelets. The cardiology team contact you for a nephrology opinion with regards to planning invasive coronary angiography. Which of the following statements best reflects your advice for minimising the risk of contrast associated AKI:

  • A. The volume of contrast during angiography should be minimised as far as possible and the patient should receive intravenous 0.9% sodium chloride both pre and post angiography.

  • B. Oral acetylcysteine should be commenced on the day of angiography and continued for 4 further days post angiography.

  • C. Intravenous acetylcysteine should be administered pre- and post-angiography.

  • D. The patient should be given 0.9% sodium chloride 6 h pre-angiography and 24 h post-angiography along with a 5-day course of oral acetylcysteine.

  • E. Use of intravenous 1.26% sodium bicarbonate has been shown to be superior to 0.9% sodium chloride for reducing contrast associated AKI when combined with other measures such as reducing the volume of contrast administered and stopping nephrotoxic drugs.

  Answer: A. The volume of contrast during angiography should be minimised as far as possible and the patient should receive intravenous 0.9% sodium chloride both pre- and post-angiography.

  • A. Correct: The volume of contrast during angiography should be minimised as far as possible and the patient should receive intravenous 0.9% sodium chloride both pre- and post-angiography. Standard measures such as minimising the contrast load and suspending nephrotoxic medications are recommended, along with adequate pre- and post-angiography hydration. Studies have shown that 0.9% sodium chloride is non-inferior to the use of sodium bicarbonate.

  • B. Incorrect: Oral acetylcysteine should be commenced on the day of angiography and continued for 4 further days post angiography. There is no evidence to support the use of acetylcysteine, it is therefore not recommended.

  • C. Incorrect: Intravenous acetylcysteine should be administered pre- and post-angiography. There is no evidence to support the use of acetylcysteine, it is therefore not recommended.

  • D. Incorrect: The patient should be given 0.9% sodium chloride 6 hours pre-angiography and 24 hours post-angiography along with a 5-day course of oral acetylcysteine. While fluids such as 0.9% sodium chloride should be given pre- and post-angiography there is no evidence for acetylcysteine.

  • E. Incorrect: Use of intravenous 1.26% sodium bicarbonate has been shown to be superior to 0.9% sodium chloride for reducing contrast associated AKI when combined with other measures such as reducing the volume of contrast administered and stopping nephrotoxic drugs. The large PRESERVE RCT evaluated patients at high risk of renal complications undergoing coronary and non-coronary angiography and found no benefit of intravenous bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of contrast associated acute kidney injury. As such, in tandem with stopping nephrotoxic medications and minimising the contrast load the most appropriate means of minimising AKI is through administration of IV 0.9% sodium chloride.

• 5. An 81-year-old gentleman is seen in the outpatient’s department. He has a background of CKD G2A2, hypertension, atrial fibrillation and heart failure with an ejection fraction of 30% on his most recent echocardiogram. He has been troubled by breathlessness which has been progressively worsening over the preceding 6 months despite up-titration of his regular furosemide. A recent 24 h holter monitor has demonstrated that his atrial fibrillation is rate controlled. His regular medications include ramipril 10 mg OD, bisoprolol 7.5 mg OD, eplerenone 25 mg OD, apixaban 2.5 mg BD and atorvastatin 80 mg OD. You send some routine bloods from clinic. Which of the following would be the most appropriate next line management?

  • A. Perform an ECG and initiate ivabradine if the heart rate is above 70 bpm.

  • B. Commence digoxin with regular monitoring of levels.

  • C. Refer for implantation of a CRT device if the ECG shows a QRS duration of >120 ms.

  • D. Stop the ramipril and switch to an ANRI.

  • E. Up-titrate the eplerenone to 50 mg OD if the serum potassium allows.

  Answer: E. Up-titrate the eplerenone to 50 mg OD if the serum potassium allows.

  • A. Incorrect: Perform an ECG and initiate ivabradine if the heart rate is above 70 bpm. Ivabradine is only indicated if the patient is in sinus rhythm, the patient in our case has atrial fibrillation so would not derive benefit from ivabradine.

  • B. Incorrect: Commence digoxin with regular monitoring of levels. Digoxin could be considered for its positive inotropy but would not be the next line choice as per the ECS Guidelines.

  • C. Incorrect: Refer for implantation of a CRT device if the ECG shows a QRS duration of >120 ms. A CRT is indicated in the presence of left bundle branch block and QRS >130 ms, not >120 ms. An ECG would be required prior to referral for CRT.

  • D. Incorrect: Stop the ramipril and switch to an ANRI. This would be a reasonable next step once his other prognostic medications had been up-titrated to the maximum dose. There is still scope to increase the eplerenone prior to ANRI initiation.

  • E. Correct: Up-titrate the eplerenone to 50 mg OD if the serum potassium allows. All medications should be up-titrated to the maximum tolerated dose prior to drug measures being added, given that there is scope to increase the eplerenone this should be the next step in managing this patient’s heart failure.

• 6. A 45-year-old with a renal transplant is seen in the transplant clinic where he reports a 1 week history of palpitations. An ECG confirms atrial fibrillation with a ventricular rate of 115 beats per minute. His blood pressure is 128/77 and other observations are within normal limits. The underlying aetiology of his renal failure is APCKD, his transplant was from a live-related donor 2 years ago and the kidney is functioning well with an eGFR of 60. His other past medical history includes hypertension and asthma and he has been admitted to hospital twice in the past 3 years with asthma exacerbations. What is the most appropriate management of his new atrial fibrillation?

  • A. Load with oral amiodarone, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo

  • B. Commence bisoprolol, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo.

  • C. Commence diltiazem, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo.

  • D. Commence bisoprolol and aspirin, check blood tests including thyroid function, book transthoracic echo.

  • E. Admit, ensure serial ECGs and troponins, load with intravenous digoxin, start anticoagulation and discharge once heart rate is less than 100 beats per minute.

  Answer: C. Commence diltiazem, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo.

  • A. Incorrect: Load with oral amiodarone, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo. Amiodarone would not be the first choice agent for rate control given its long term side effects of thyroid dysfunction and pulmonary fibrosis. It is reserved for cases resistant to standard therapies. The other management steps are correct.

  • B. Incorrect: Commence bisoprolol, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo. Bisoprolol would be contraindicated given this patient’s severe asthma (2 hospital admissions in past 3 years). The other management steps are correct.

  • C. Correct: Commence diltiazem, counsel regarding anticoagulation, check blood tests including thyroid function, book transthoracic echo. Given this patient’s asthma, a non-dihydropyridine calcium channel blocker would be the recommended first line agent to control rate.

  • D. Incorrect: Commence bisoprolol and aspirin, check blood tests including thyroid function, book transthoracic echo. Bisoprolol would be contraindicated given this patient’s severe asthma (2 hospital admissions in past 3 years). The other management steps are correct. There is no role for aspirin in managing stroke risk, if the CHADSVASC score is 1 or above then the options are warfarin or DOAC.

  • E. Incorrect: Admit, ensure serial ECGs and troponins, load with intravenous digoxin, start anticoagulation and discharge once heart rate is less than 100 beats per minute. This patient is stable and does not require hospital admission nor intravenous digitalisation. There is no evidence of an acute coronary syndrome to warrant serial ECGs or troponin measurements. The European Society of Cardiology recommend targeting a heart rate of <110 beats per minute in the management of atrial fibrilation. There is no evidence to support tighter rate control than this.

• 7. With regards to revascularisation options in a patient with symptomatic multivessel coronary artery disease, which of the following statements is true?

  • A. In non-dialysis patients with CKD, there is a higher risk of short-term AKI with PCI than with CABG.

  • B. In the long-term the risk of needing repeat revascularisation in the future is higher with PCI than with CABG

  Answer B. CABG is associated with lower risk of revascularisation (and higher short term risks)

• 8. A 50 year man with heart failure (EF 35%), diabetes and CKD stage 3 on Metformin, Ramipril, Eplerenone and Bisoprolol, presented with poor blood sugar control. What is next best choice of medication?

  • A. Empagliflozin

  • B. Gliclazide

  • C. Insulin

  • D. Pioglitazone

  • E. Sitagliptin

  Answer: A. Empagliflozin which is evidenced based therapy to improve outcomes.

• 9. The 50 year above patient has a potassium of 5.9 mmol/L and suffering from bilateral leg oedema. What is next best treatment for fluid overload

  • A. Amiloride

  • B. Furosemide

  • C. Haemodialysis

  • D. Peritoneal dialysis

  • E. Spironolactone

  Answer: B. Furosemide and it will decrease serum potassium and treat fluid overload.

• 10. The 50-year-old above patients potassium continues to rise. What is next treatment to will you consider to treat hyperkalaemia

  • A. Stop bisoprolol

  • B. Stop metformin

  • C. Stop ramipril

  • D. Start sodium zirconium cyclosilicate

  • E. Stop spironolactone

  Answer: D. May be the right answer if sodium zirconium cyclosilicate is available. Alternatively, the spironolactone/ramipril could be stopped/reduced.

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