Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease

Abstract

Background: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD.

Methods: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m², referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m² (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters.

Results: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049).

Conclusions: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Keywords: Cardiovascular events; Cardiovascular magnetic resonance; Chronic kidney disease; Myocardial ischemia; Prognosis; Stress testing; Unrecognized myocardial infarction.

Fig. 1

Study flowchart. CKD chronic kidney disease; CMR cardiovascular magnetic resonance; CVD cardiovascular disease; ECG electrocardiogram

Fig. 2

Examples of inducible myocardial ischemia on stress CMR in patients with known CKD. A normal. 77-year-old male with hypertension and history of CKD (GFR 38 ml/min/m²), presenting atypical angina. Stress CMR revealed no perfusion defect and LGE was negative, ruling out the diagnosis of myocardial ischemia. B Inducible ischemia. 69-year-old female with and history of CKD (GFR 56 ml/min/m²), presenting dyspnea on exertion. First-pass myocardial stress perfusion images revealed a reversible perfusion defect of the anteroseptal wall (white arrows) without LGE, indicative of myocardial inducible ischemia suggestive of significant LAD stenosis, confirmed by coronary angiography. C Myocardial scar without ischemia. 70-year-old female with diabetes mellitus, hypertension and history of CKD (GFR 41 ml/min/m²), presenting dyspnea on exertion. Stress CMR showed a subendocardial lateral scar on LGE (orange arrows), with a colocalization of the perfusion defect (white arrows) and, therefore, no inducible ischemia. Coronary angiography confirmed the absence of significant stenosis. D Myocardial scar with additional inducible ischemia. 67-year-old male with diabetes mellitus, hypertension and history of CKD (GFR 55 ml/min/m²), presenting atypical angina. Stress CMR showed a subendocardial scar on the antero-septo-apical wall on LGE sequences (orange arrows), and a perfusion defect of the inferior and infero-septal wall (white arrows) on first-pass perfusion images, indicative of inducible myocardial ischemia. Coronary angiography revealed high-grade stenoses of the RCA. CAD coronary artery disease; CMR cardiovascular magnetic resonance; Cx circumflex coronary artery; LAD left anterior descending; LGE late gadolinium enhancement; MI myocardial infarction; NSTEMI non-ST segment elevation myocardial infarction; PCI percutaneous coronary intervention; RCA right coronary artery; STEMI ST segment elevation myocardial infarction

Fig. 3

Cumulative rates of MACE during follow-up stratified by the presence or absence of inducible ischemia and by the presence or absence of unrecognized myocardial infarction (MI)

Fig. 4

Cumulative rates of MACE during follow-up stratified by the extent of inducible ischemia. Mild, moderate, and severe ischemia were defined as the involvement of 1 to 2, 3 to 5, and ≥ 6 myocardial segments, respectively. Comparison tests were based on the Cochran-Armitage test for trend

Fig. 5

Kaplan–Meier curves for MACE (A) and Cardiovascular mortality (B) stratified by the presence of inducible ischemia. Test comparing the two groups is based on the log-rank test

Fig. 6

Subgroup analysis. Forest-plot of incidence of MACE based on the presence of silent ischemia in prespecified subgroups. *N events/N subgroup: number of patients who had a major adverse clinical event (MACE)/number of patients in the subgroup

Fig. 7

Competing risk analysis. Cumulative incidence functions of nonfatal MI (A) and cardiovascular mortality without nonfatal MI (B)