Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults

Abstract

Aims Non-ischaemic cardiomyopathies (NICM) can cause heart failure and death. Cardiac magnetic resonance (CMR) detects myocardial scar/fibrosis associated with myocardial infarction (MI) and NICM with late gadolinium enhancement (LGE). The aim of this study was to determine the prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in a community-based sample of older adults. Methods and results The ICELAND-MI cohort, a substudy of the Age, Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) study, provided a well-characterized population of 900 subjects after excluding subjects with pre-existing heart failure. Late gadolinium enhancement CMR divided subjects into four groups: MI (n = 211), major (n = 54) non-ischaemic fibrosis (well-established, classic patterns, associated with myocarditis, infiltrative cardiomyopathies, or pathological hypertrophy), minor (n = 238) non-ischaemic fibrosis (remaining localized patterns not meeting major criteria), and a no LGE (n = 397) reference group. The primary outcome was time to death or first heart failure hospitalization. During a median follow-up of 5.8 years, 192 composite events occurred (115 deaths and 77 hospitalizations for incident heart failure). After inverse probability weighting, major non-ischaemic fibrosis [hazard ratio (HR) 3.2, P < 0.001] remained independently associated with the primary endpoint, while MI (HR 1.4, P = 0.10) and minor non-ischaemic LGE (HR 1.2, P = 0.39) did not. Major non-ischaemic fibrosis was associated with a poorer outcome than MI (HR = 2.3, P = 0.001) in the adjusted analysis. Conclusion Major non-ischaemic patterns of myocardial fibrosis portended worse prognosis than no fibrosis/scar in an older community-based cohort. Traditional risk factors largely accounted for the effect of MI and minor non-ischaemic LGE.

Ischemic and non-ischemic patterns of late gadolinium enhancement in heart failure with reduced ejection fraction

“…Cardiovascular risk stratification is important and could be improved by the use of biomarkers or data from Holter electrocardiogram recordings [37][38][39]. Some studies have demonstrated that the presence of LGE predicts poor clinical outcomes such as hospitalization due to HF, fatal ventricular arrhythmias, and SCD, in patients with either an ischemic or nonischemic etiology of HF [8,26,[40][41][42][43][44]. Non-ischemic HF etiology is one of the predictors of LVEF recovery [45].…”

“…Non-ischemic HF etiology is one of the predictors of LVEF recovery [45]. However, a recently adjusted analysis has shown that major nonischemic fibrosis was related to worse clinical outcomes than MI [8]. The presence of LGE was found to be associated with appropriate ICD therapy.…”

“…LGE this is typically subendocardial or transmural [7]. Non-ischemic myocardial injury can be observed at the epicardium, in the mid-wall, or at insertion points [5,7,8]. Moreover, LGE has been found to predict clinical outcomes in selected patients undergoing ICD placement [9].…”

“…1B). The left anterior descending coronary artery (LAD) supplies segments 1,2,7,8,13,14, and 17, the right coronary artery (RCA) supplies segments 3, 4, 9, 10, and 15, while the left circumflex coronary artery (LCx) supplies segments 5, 6, 11, 12, and 16 [11]. However, coronary arteries may be anomalous and their anatomy varies from patient to patient, creating a limitation of the AHA model [12][13][14][15].…”

Cell Cycle Arrest-Driven Fibrosis

“…2) Fibrosis is the excessive accumulation of extracellular matrix (ECM) and is related to a poor prognosis, because excessive fibrosis can lead to increased left ventricular wall stiffness and decreased mechanoelectric coupling. 3,4) There are several well-known mediators that induce cardiac fibrosis, such as transforming growth factor (TGF), Wnt signaling, and the renin-angiotensinaldosterone system. 5) Though the inhibition of these signaling pathways may be beneficial in anti-fibrotic therapies, few drugs targeting them are used in clinical practice.…”