Implications of chronic kidney disease on presentation, treatment and outcomes in patients with aortic stenosis

Abstract

Background: Aortic valve stenosis (AS) is the most common valvular heart disease in the western world. No pharmacological treatment has been proved to halt the progression to severe disease and after symptom debut, the prognosis is poor with a high mortality, if left untreated. Hence, surgical or transcatheter aortic valve replacement (AVR) is the only therapeutic option for severe AS. AS is prevalent with rapid evolution among patients with chronic kidney disease (CKD). Concomitant AS and CKD is accompanied with high risk of death and cardiovascular events.

The aims of this thesis were to: 1. Assess whether CKD is associated with the risk of developing AS in a general population; 2. Determine the risk factors of worsening renal function following transcutaneous AVR (TAVR) and its association with the short and long-term mortality; 3. Evaluate the point prevalence of AS and AVR at dialysis start, and to assess the incidence rates and associated risk factors for new onset AS after dialysis initiation; and 4. Compare the long-term complication rates after surgical AVR (SAVR) with mechanical (MAV) or bioprosthetic aortic valve (BAV) in dialysis patients.

Methods and results: Study I. Kidney Dysfunction and the risk of developing Aortic stenosis The study included all adult Stockholm citizens from the Stockholm CREAtinine Measurement project (SCREAM) with known kidney function and without prior diagnosis of AS, and the aim was to study the risk of AS in relation to kidney function. Kidney dysfunction was found to be independently associated with higher risk of developing AS. This risk increased linearly with lower estimated Glomerular Filtration Rate (eGFR) and was present after adjustments of covariates.

Study II. Risk factors for worsening renal function and their association with long-term mortality following transcatheter aortic valve implantation: data from the SWEDEHEART registry. We used the The SWEdish traNscatheter cardiac intervention regisTRY (SWENTRY), part of Swedish Web-system for Enhancement and Development of Evidencebased care in Heart disease Evaluated According to Recommended Therapies (SWEDHEART) to identify all patients with severe AS who underwent TAVR. Risk factors associated with persistent acute kidney injury (pAKI) were explored, and their association to short- and long-term mortality was explored. pAKI occurred in 6.1% of AS patients who underwent TAVR and was associated with a doubled short- and long-term risk of death, independent of baseline kidney function. Male gender, baseline kidney function and transapical access were found to be independently associated with pAKI.

Study III. Epidemiology of aortic stenosis/aortic valve replacement in the nationwide Swedish Renal Registry. The Swedish Renal Registry (SNR), a national registry of all patients who commenced dialysis or received a kidney transplant in Sweden between 1993 and 2018, was used to identify the point prevalence of AS and AVR at dialysis start, and to explore the incidence and associated factors for developing AS and AVR after dialysis initiation. We found that patients initiating dialysis have high prevalence and occurrence of AS. Older age, male gender, hypertension, and peritoneal dialysis were strongly associated with new onset AS. Only 20% of new cases with incident AS underwent AVR.

Study IV. Prognosis after aortic valve replacement in dialysis patients – a report from the Swedish Renal Registry. We identified all dialysis patients in the SNR registry who had undergone surgical AVR with MAV or BAV. We compared the long-term complication rates of the composite end-point of all-cause death, bleeding, stroke and aortic valve reoperation, and separately, the end-point all-cause death. The main finding was that BAV- and MAV-recipients had comparable mortality and complication rates.

Conclusions: Kidney dysfunction is independently associated with new onset AS in a general population. This association was attenuated, but remained significant after adjustments, and the association increased linearly with lower eGFR categories. In unselected patients with severe AS undergoing TAVR, worsening kidney function occurred often, and was predicted by male gender, baseline kidney dysfunction and access type. pAKI was strongly associated with higher risk of all-cause death. Among dialysis patients, the prevalence at initiation and occurrence of clinically detected AS was high, but few underwent AVR. Dialysis patients who underwent surgical AVR with MAV or BAV had similar rates of all-cause death and overall complication rates.