Pub Date: Thursday, May 13, 2021
Author: Blase Carabello
Affiliation: East Carolina University and Vidant Medical Center
Chronic kidney disease (CKD) affects prognosis in almost every other medical condition in which it is present. An apparently healthy, fit sixty-year-old man has a life expectancy of about 20 - 25 years. For a sixty-year-old man with CKD stage 3a, life expectancy is 14 years, for stage 3b it is 8 years, for stage 4 life expectancy is 6 years, and for end stage renal disease it is just <5 years 1,2. For a seventy-year-old apparently healthy man, life expectancy is about 15 years. For a seventy-year-old man with CKD stage 3a, life expectancy is 8 years, for stage 3b it is 6 years, for stage 4 life expectancy is 4 years and for end stage renal disease it is just 3.5 years. For women life expectancy, is about 1-4 years greater for each of the above categories.
Severe symptomatic aortic stenosis (AS) is by itself a fatal illness with only a 25 % 3year survival unless treated with aortic valve replacement (AVR)3. Not surprisingly the combination of these 2 morbid illnesses, CKD and AS, have major impacts on each other as so thoroughly discussed by Shroff et al in their AHA scientific statement: Evaluation and Management of Aortic Stenosis in Chronic Kidney Disease4. The authors do a wonderful job in eliciting potential mechanisms for the effects of CKD on AS, the strengths and limitations of the diagnostic modalities at our disposal and the impact of CKD on AVR. They are also quick to point out that the data we do have come from subset analysis of randomized trials and registries aimed at tracking AS. There are no trials that directly randomize patients with combined AS and CKD to different 2 different therapies or randomize patients with AS alone versus combined disease to a specific therapy, obviously adding uncertainty to inferences made about the interaction of the two diseases.
When and how much should CKD affect AVR management?
It would be an unusual week when a patient with combined CKD and AS isn’t discussed at most Heart Team meetings. For patients with CKD 3, the issue of contrast-induced nephropathy and how to minimize it, well discussed by Shroff et al., frequently arises. For more advanced CKD, the intersection of mortality from AS and that of CKD becomes the major focus of discussion. For a seventy-five-year-old man receiving dialysis, life expectancy is 3.5 years while for symptomatic severe AS it is 2 years, reducing the expected larger mortality benefit from AVR in such patients. How much quality and quantity of life is afforded by surgical AVR (SAVR) or transcatheter AVR (TAVR) in such cases? With little data to guide us, it is the Heart Team’s job to make this assessment on a case-by-case basis.
The role of symptoms
As noted above and as is widely understood, the presence of symptoms dramatically worsens the prognosis of AS 5,6. It now seems clear that many “asymptomatic” AS patients also benefit from AVR 5-8, However, it is unknown whether asymptomatic AS patients with CKD also might benefit from early AVR. When symptoms are present, understanding their origin in CKD is complex. Syncope and angina with angiographically normal epicardial coronary arteries comprise a minority of the symptoms accounted for in elderly patients with AS and CKD but when they do occur, the likely culprit is AS. Unfortunately, dyspnea is the most common presenting symptom for these patients. But as noted by Shroff et al, in CKD patients there is a catch. Most such patients have longstanding hypertension and the left ventricular hypertrophy that accompanies it, inevitably invoking left ventricular diastolic dysfunction and dyspnea. The obvious conundrum becomes whether the patient’s dyspnea is due to AS or CKD or a combination of both. Obviously if CKD is the only cause of the patient’s symptoms, AVR is unlikely to improve the patient’s quality of life. In dialysis patients, the issue is even more complex because volume status and the symptoms of volume overload are controlled externally by the amount of volume removed at each treatment session, as opposed to the disease process itself. The challenge is magnified because CKD reduces the mortality benefit of AVR in AS, making improvement in the quality of life with improvement in symptoms a progressively more important focus of therapy
Clues from the history
A careful history may help the provider navigate this Charybdis and Scylla. If the symptom of dyspnea appeared when the AS was mild or moderate in severity, it suggests that AS was not its cause. On the other hand, the relatively abrupt onset of dyspnea may indicate that it coincides with worsened AS. The relative sudden onset of dialysis intolerance in CKD 5 patients may point to the hemodynamic consequences of now severe AS and the need to relieve it, helping to guide therapy.
The commonly employed biomarkers, troponin and natriuretic peptides may be elevated in AS and have negative prognostic impact 9-11. However, CKD affects excretion of troponin and reduces its prognostic value in the low abnormal range. Natriuretic peptides may be elevated in AS and elevation is a negative prognostic marker but elevations in CKD may be due to abnormal volume handling not related to AS reducing the prognostic value of BNP and N-T pro BNP.
Right heart catheterization
Patients considered for AVR usually undergo cardiac catheterization prior to the procedure to assess coronary anatomy because of the high coincidence of AS and coronary artery disease. Most patients with CKD should also undergo right heart catheterization at the same time. Both AS and hypertension accompanying CKD lead to LVH and elevated filling pressures and right heart catheterization can’t distinguish which of the two is the cause of a patient’s dyspnea. However, if filling pressures are normal both at rest and with exercise in the cath lab, it raises the likelihood that the dyspnea has an extra-cardiac cause and that the benefit of AVR in relieving dyspnea is limited.
Balloon aortic valvotomy
Balloon aortic valvotomy has been use as a diagnostic tool especially in low flow low gradient AS 12. The concept is simple… if the slight relief of AS that BAV provides, improves symptoms, AVR that provides better hemodynamic results than BAV is more likely to be successful. The data supporting the role of BAV in AS are modest. To be sure they are even more scant in patients with CKD and AS. However, if BAV improves the patients’ symptoms, it is logical to suspect that AS is the culprit and that the patient may benefit from AVR
The benefit of AVR in patients with severe AS in unquestioned because of the substantial data that support it. Unfortunately, the co-presence of CKD complicates the evaluation of such patients, impacts AVR itself and impacts prognosis later in life. Shroff and colleagues perform for us a great service by bringing us up to date on the interaction of these 2 diseases. Even after their excellent review, the limited data in patients with combined disease leaves us with uncertainty as to the decision regarding AVR in such patients. Judgment about in whom and when to provide AVR for patients with combined AS and CKD will fall upon the Heart Team to use the data which we do have and the personal knowledge of each patient to make the best decision for the patient.
Shroff GR, Bangalore S, Bhave NM, Chang TI, Garcia S, Mathew RO, Rangaswami J, Ternacle J, Thourani VH, Pibarot P; on behalf of the American Heart Association Council on the Kidney in Cardiovascular Disease and Stroke Council. Evaluation and management of aortic stenosis in chronic kidney disease: a scientific statement from the American Heart Association [published online ahead of print May 13, 2021]. Circulation. doi: 10.1161/CIR.0000000000000979
- Neild GH. Life Expectancy with Chronic Kidney Disease: An Educational Review. Pediatric Nephrology.2017;32:243-248.
- Turin TC, Tonelli M, Manns BJ, Ravani P, Ahmed SB, Hemmelgarn BR. Chronic kidney disease and life expectancy. Nephrol Dial Transplant. 2012, 27:3182.
- Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-607.
- Shroff GR, Bangalore S, Bhave NM, Chang TI, Garcia S, Mathew RO, Rangaswami J, Ternacle J, Thourani VH, Pibarot P; on behalf of the American Heart Association Council on the Kidney in Cardiovascular Disease and Stroke Council. Evaluation and management of aortic stenosis in chronic kidney disease: a scientific statement from the American Heart Association [published online ahead of print May 13, 2021]. Circulation. doi: 10.1161/CIR.0000000000000979
- Rosenhek R, Zilberszac R, Schemper M, Czerny M, Mundigler G, Graf S, Bergler-Klein J, Grimm M, Gabriel H, Maurer G. Natural history of very severe aortic stenosis. Circulation. 2010;121:151-6.
- Bonow RO, O'Gara PT. Aortic Stenosis-50 Years of Discovery. JAMA Cardiol. 2018 Dec 1;3(12):1141-1143.
- Saeed S, Rajani R, Seifert R, Parkin D, Chambers J. Exercise testing in patients with asymptomatic moderate or severe aortic stenosis. Heart. 2018;104:1836-42.
- Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020 Dec 17:S0735-1097(20)37796-2.
- Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H, Binder T, Pacher M, Maurer g, Baumgartner H. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation. 2004;109:2302-8
- Clavel MA, Malouf J, Michelena HI, Suri RM, Jaffe AS, Mahoney DW, Enriquez-Sarano M. B-type natriuretic peptide clinical activation in aortic stenosis: impact on long-term survival. J Am Coll Cardiol. 2014 May 20;63(19):2016-25.
- Spampinato RA, Sieg F, Weiss S, Kornej J , Haunschild J , von Aspern K, Strotdrees E, Noack T, Lehmann S, Etz C, Borger MA. Multi-biomarker mortality prediction in patients with aortic stenosis undergoing valve replacement J Cardiol. 2020 Aug;76(2):154-162.
- Szerlip M, Arsalan M, Mack MC, Filardo G, Worley C, Kim RJ, Phan T, Pollock B, Rangel C, Brown DL, Mack M, Holper EM. Usefulness of balloon aortic valvuloplasty in the management of patients with aortic stenosis. Am J Cardiol. 2017;120:1366-72
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