Evaluation of alterations in cardiovascular structure and function in end-stage renal failure.
Background: Chronic renal dysfunction is associated with myriad alterations in cardiovascular structure and function, resulting in markedly elevated rates of cardiac and vascular morbidity and mortality. Utilising advances in cardiovascular magnetic resonance imaging (CMR), we evaluated the cardiovascular sequelae of arterio-venous fistula formation in advanced chronic kidney disease, and the impact of elective arterio-venous fistula ligation following successful renal transplantation. Furthermore, we undertook to evaluate the diagnostic accuracy of dobutamine-stress CMR in the detection of haemodynamically‐significant coronary artery disease prior to renal transplantation. Finally, we invasively evaluated coronary endothelial function in the presence of advanced renal dysfunction, and compared this to subjects with preserved renal function. Methods / Results: Study 1: CMR was undertaken to evaluate cardiac structure and function, brachial artery endothelial function (as assessed by flow-mediated dilatation) and aortic distensibility in tweny‐four subjects at baseline, and 6‐months following, clinically indicated arterio‐venous fistula creation in preparation for the commencement of haemodialysis for end-stage renal failure. Following arterio‐venous fistula creation, mean cardiac output increased by 25.0% (p<0.0001), with substantial associated increases in left and right ventricular volumes, left and right atrial area and left ventricular mass (12.7% increase, p<0.0001). Peripheral endothelial function was significantly impaired at follow-up (9.0 ±9% vs. 3.0 ±6%, p=0.01). No significant change in aortic distensibility was identified. Study 2: Cardiac and vascular function were similarly assessed utilising CMR in eighteen subjects prior to, and 6‐months following, clinically indicated arterio-venous fistula ligation in the context of successful, stable renal transplantation. Following AVF-ligation, mean cardiac output fell by 15.6% (p=0.004), with significant attendant decreases in atrial and ventricular chamber dimensions. Notably, left ventricular mass fell by 9.7% (p=0.0001) at follow‐up. Aortic distensibility was unchanged following AVF‐ligation, though endothelial function improved significantly (2.5 ±6.5% vs. 8.0 ±5.9%, p=0.043). Study 3: Dobutamine-stress CMR was performed in twenty‐one subjects prior to clinically‐indicated invasive coronary angiography before potential renal transplantation. Dobutamine-stress CMR demonstrated 100% sensitivity and 93% specificity for the detection of angiographically significant coronary disease (≥70% stenosis severity). This compared favourably to results for the institutional‐standard (SPECT: sensitivity 67%, specificity 38%; p<0.0001 compared to CMR). Study 4: At invasive coronary angiography, endothelium‐dependent and endothelium–independent coronary endothelial and microvascular function were evaluated amongst eight pre‐renal transplant subjects with only minimal coronary artery disease (≤20% epicardial coronary stenoses). Utilising intra-coronary infusions of acetylcholine (10⁻⁷M and 10⁻⁶M), adenosine (48mcg) and glyceryl tri‐nitrate (100mcg), results were compared to thirteen control subjects with minimal coronary artery disease but comparatively preserved renal function. There was no significant difference in endothelium‐dependent or endothelium–independent coronary endothelial function between the cohorts. Microvascular function (as assessed by coronary flow reserve following adenosine administration) was markedly impaired in subjects with advanced renal impairment compared to controls (1.9 ±0.4 vs. 3.0 ±1.1, p=0.01). Conclusions: Chronic kidney disease is associated with substantial alterations in cardiovascular structure and function. Arterio‐venous fistulae, though necessary for the performance of haemodialysis, appear to contribute significantly to the high burden of cardiovascular maladaptation present in this condition. Recent advances in CMR and stress‐CMR may play a significant role in improving the detection of sub-clinical cardiovascular disease in these high‐risk patients.
end stage renal failure; cardiovascular imaging
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