Aortic stiffness is independently associated with interstitial myocardial fibrosis by native T1 and accelerated in the presence of chronic kidney disease

Mengzhen Chen, Luca Arcari, Juergen Engel, Tilo Freiwald, Steffen Platschek, Hui Zhou, Hafisyatul Zainal, Stefan Buettner, Andreas M Zeiher, Helmut Geiger, Ingeborg Hauser, Eike Nagel, Valentina O Puntmann, Mengzhen Chen, Luca Arcari, Juergen Engel, Tilo Freiwald, Steffen Platschek, Hui Zhou, Hafisyatul Zainal, Stefan Buettner, Andreas M Zeiher, Helmut Geiger, Ingeborg Hauser, Eike Nagel, Valentina O Puntmann

Abstract

Background: Patients with chronic kidney disease (CKD) have considerable cardiovascular morbidity and mortality. Aortic stiffness is an independent predictor of cardiovascular risk and related to left ventricular remodeling and heart failure. Myocardial fibrosis is the pathophysiological hallmark of the failing heart.

Methods and results: An observational study of consecutive CKD patients (n = 276) undergoing comprehensive clinical cardiovascular magnetic resonance imaging. The relationship between aortic stiffness, myocardial fibrosis, left ventricular remodeling and the severity of chronic kidney disease was examined. Compared to age-gender matched controls with no known kidney disease (n = 242), CKD patients had considerably higher myocardial native T1 and central aortic PWV (p ≪ 0.001), as well as abnormal diastolic relaxation by E/e' (mean) by echocardiography (p ≪ 0.01). A third of all patients had LGE, with similar proportions for the presence and the (ischaemic and non-ischaemic) pattern between the groups. PWV was strongly associated with and age, NT-proBNP and native T1 in both groups, but not with LGE presence or type; the associations were amplified in severe CKD stages. In multivariate analyses, PWV was independently associated with native T1 in both groups (p ≪ 0.01) with near two-fold increase in adjusted R2 in the presence of CKD (native T1 (10 ms) R2, B(95%CI) CKD vs. non-CKD 0.28, 0.2(0.15-0.25) vs. 0.18, 0.1(0.06-0.15), p ≪ 0.01).

Conclusions: Aortic stiffness and interstitial myocardial fibrosis are interrelated; this association is accelerated in the presence of CKD, but independent of LGE. Our findings reiterate the significant contribution of CKD-related factors to the pathophysiology of cardiovascular remodeling.

Keywords: Aortic stiffness; Chronic kidney disease; Native T1 mapping.

Conflict of interest statement

No conflict of interests.

Figures

Fig. 1
Fig. 1
CMR imaging protocol, consisting of native T1 mapping, stress-myocardial perfusion for relevant myocardial ischaemia. Cine-imaging for cardiac volumes and LV mass, late gadolinium enhancement and PWV for central aortic stiffness. Rest myocardial perfusion was not performed in line with restricted allowance of GBCA in CKD [21,22].
Fig. 2
Fig. 2
Aortic stiffness and diffuse myocardial fibrosis are negatively associated with severity of CKD. Bivariate associations between native T1 and PWV with eGFR (r = −0.31 and r = −0.44, p ≪ 0.001, respectively).
Fig. 3
Fig. 3
Associations between aortic stiffness and markers of diffuse myocardial fibrosis, stiffness and remodeling are potentiated with severity of CKD. Bivariate correlations between PWV and native T1, E/e′ (mean), LV mass index and LV-EF.
Fig. 4
Fig. 4
Pulse wave velocity correlations and CKD Stages (Table 3). Native T1 has the strongest association with PWV in all stages, followed by E/e′, LVmass in stage 3 and LV-EF in stage 4. *p ≪ 0.05, **p ≪ 0.01.

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