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- Hedman, A. K., et al.
(författare)
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Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:5, s. 342-349
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Tidskriftsartikel (refereegranskat)abstract
- Objective Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups. Methods We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71-83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses. Results We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95%CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8-2.9); 5.7 (2.6-12.8); 2.9 (1.5-5.6); 2.7 (1.6-4.6); 2.1 (1.2-3.9)). Conclusions Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.
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| 2. |
- Hage, C., et al.
(författare)
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Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients
- 2020
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:4, s. 1534-1546
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Tidskriftsartikel (refereegranskat)abstract
- Aims In heart failure (HF) with preserved ejection fraction (HFpEF), microvascular inflammation is proposed as an underlying mechanism. Myeloperoxidase (MPO) is associated with vascular dysfunction and prognosis in congestive HF. Methods and results MPO, MPO-related biomarkers, and echocardiography were assessed in 86 patients, 4-8 weeks after presentation with acute HF (EF >= 45%), and in 46 healthy controls. Patients were followed up for median 579 days (Q1;Q3 276;1178) regarding the composite endpoint all-cause mortality or HF hospitalization. Patients were 73 years old, 51% were female, EF was 64% (Q1;Q3 58;68), E/e ' was ratio 10.8 (8.3;14.0), and left atrial volume index (LAVI) was 43 mL/m(2) (38;52). Controls were 60 (57;62) years old (vs. patients; P < 0.001), 24% were female (P = 0.005), and left ventricular EF was 63% (59;66; P = 0.790). MPO was increased in HFpEF compared with controls, 101 (81;132) vs. 86 (74;101 ng/mL, P = 0.015), as was uric acid 369 (314;439) vs. 289 (252;328 mu mol/L, P < 0.001), calprotectin, asymmetric dimethyl arginine (ADMA), and symmetric dimethyl arginine (SDMA), while arginine was decreased. MPO correlated with uric acid (r = 0.26; P = 0.016). In patients with E/e ' > 14, uric acid and SDMA were elevated (421 vs. 344 mu M, P = 0.012; 0.54 vs. 0.47 mu M, P = 0.039, respectively), and MPO was 121 vs. 98 ng/mL (P = 0.090). The ratios of arginine/ADMA (112 vs. 162; P < 0.001) and ADMA/SDMA (1.36 vs. 1.17; P = 0.002) were decreased in HFpEF patients, suggesting reduced NO availability and increased enzymatic clearance of ADMA, respectively. Uric acid independently predicted the endpoint [hazard ratio (HR) 3.76 (95% CI 1.19-11.85; P = 0.024)] but not MPO [HR 1.48 (95% CI 0.70-3.14; P = 0.304)] or the other biomarkers. Conclusions In HFpEF, MPO-dependent oxidative stress reflected by uric acid and calprotectin is increased, and SDMA is associated with diastolic dysfunction and uric acid with outcome. This suggests microvascular neutrophil involvement mirroring endothelial dysfunction, a central component of the HFpEF syndrome and a potential treatment target.
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