Importance of structural heart disease and diastolic dysfunction in heart failure with preserved ejection fraction assessed according to the ESC guidelines - A substudy in the Ka (Karolinska) Ren (Rennes) study

Persson, Hans; Donal, Erwan; Lund, Lars H.; Matan, Dmitri; Oger, Emmanuel; Hage, Camilla; Daubert, Jean‐Claude; Linde, Cecilia; Investigators, KaRen

doi:10.1016/j.ijcard.2018.06.078

Cited by 13 publications

(10 citation statements)

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“…There was a difference in age and gender between the patients and the healthy controls. Further, the protocol did not require structural heart disease or diastolic dysfunction as it was designed prior to the 2012 and 2016 ESC guidelines; however, 94% of the study population did comply with the present criteria of HFpEF as recommended by ESC 2016 guidelines 41 . We analysed several biomarkers as reflectors of inflammation, endothelial function, and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Further, the protocol did not require structural heart disease or diastolic dysfunction as it was designed prior to the 2012 and 2016 ESC guidelines; however, 94% of the study population did comply with the present criteria of HFpEF as recommended by ESC 2016 guidelines. 41 We analysed several biomarkers as reflectors of inflammation, endothelial function, and oxidative stress. We do, however, acknowledge that additional biomarkers such as 4-hydroxy-2-nonenal or 3-nitrotyrosine would provide even more evidence of oxidative and nitrosative stress.…”

Section: Uric Acid As a Reflector Of Myeloperoxidasementioning

confidence: 99%

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Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients

et al. 2020

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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 μmol/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 μM, P = 0.012; 0.54 vs. 0.47 μM, 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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Section: Discussionmentioning

confidence: 99%

Section: Uric Acid As a Reflector Of Myeloperoxidasementioning

confidence: 99%

Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients

et al. 2020

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“…Natriuretic peptides and echocardiography are increasingly available (although not always used) both in the acute setting and at follow‐up, enabling diagnosis establishment and use of combined measures for prognostic assessment. The echocardiographic HFpEF criteria have evolved to include the combination of high filling pressures with structural changes such as LAVI and LV hypertrophy or mass, and we have previously shown in KaRen that ESC echocardiography criteria were present in 76% of stable HFpEF and E/é in stable HFpEF predicted outcomes . In contrast, in the present study focusing on FC‐HF, the E/é criteria for HFpEF were part of descriptive model 3 but did not add prognostic information compared with structural changes alone as descriptive model 4 (derived from the PARAGON trial) …”

Section: Discussionmentioning

confidence: 69%

Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction

et al. 2019

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Aims This study aims to assess prognostic impact of Framingham criteria for heart failure (FC‐HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results In the prospective Karolinska‐Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all‐cause mortality and HF hospitalization. The descriptive models were FC‐HF alone, FC‐HF + natriuretic peptides (NPs) according to the PARAGON trial, FC‐HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC‐HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4–8 weeks, 13 (2.4%) patients died before the planned follow‐up, and 88 patients (16%) declined or were unable to return. Three hundred ninety‐nine patients have FC registered at follow‐up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC‐HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1–4 had to fulfil the FC‐HF. The patients in model 0 did not fulfil the criteria for FC‐HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47–7.76, P = 0.004]. Patients without FC‐HF had better prognosis than patients meeting FC‐HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14–2.09, P = 0.005; HR 1.71, 95% CI 1.24–2.36, P = 0.002; HR 1.95, 95% CI 1.36–2.81, P = 0.001; and HR 2.05, 95% CI 1.45–2.91, P < 0.001, for descriptive models 1–4, respectively. No descriptive model independently predicted the endpoint. Conclusions In ambulatory HFpEF patients, a quarter met FC‐HF, while most met NP and echocardiography criteria for HF. Residual FC‐HF tended to be associated with increased risk for mortality and HF hospitalization, further strengthened by NPs and echocardiographic criteria, highlighting its role in clinical risk assessment.

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“…In a prospective HFpEF registry, only moderate to severe diastolic dysfunction and a high number (�4) of abnormal diastolic parameters were associated with worse prognosis over short term followup (i.e. 4-8 weeks) [18]. In an echocardiographic substudy of the Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction (PARAGON-HF) trial, wall thickness, mass, E/e' ratio, tricuspid regurgitation velocity, and enlarged right ventricular size were associated with HF readmission or cardiovascular death [31].…”

Section: Plos Onementioning

confidence: 99%

“…Despite the frequency of HF hospitalization, prediction of individuals at high risk for future rehospitalization remains difficult using traditional approaches [7]. While many echocardiographic variables such as left ventricular (LV) wall thickness, mass, and chamber sizes, have been associated with an adverse prognosis in individuals with prior heart failure hospitalization [8], only a few studies have evaluated the ability of these variables to predict HF readmission in a mixed systolic function cohort [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Thus, whether there is a significant interaction between LV systolic function category and the relative importance of individual echocardiographic variables in driving HF readmission risk remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Retrospective evaluation of echocardiographic variables for prediction of heart failure hospitalization in heart failure with preserved versus reduced ejection fraction: A single center experience

Hammond

Shen

et al. 2020

PLoS ONE

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Background Limited data exist on the differential ability of variables on transthoracic echocardiogram (TTE) to predict heart failure (HF) readmission across the spectrum of left ventricular (LV) systolic function. Methods We linked 15 years of TTE report data (1/6/2003-5/3/2018) at Beth Israel Deaconess Medical Center to complete Medicare claims. In those with recent HF, we evaluated the relationship between variables on baseline TTE and HF readmission, stratified by LVEF. Results After excluding TTEs with uninterpretable diastology, 5,900 individuals (mean age: 76.9 years; 49.1% female) were included, of which 2545 individuals (41.6%) were admitted for HF. Diastolic variables augmented prediction compared to demographics, comorbidities, and echocardiographic structural variables (p < 0.001), though discrimination was modest (c-statistic = 0.63). LV dimensions and eccentric hypertrophy predicted HF in HF with reduced (HFrEF) but not preserved (HFpEF) systolic function, whereas LV wall thickness, NT-proBNP, pulmonary vein D- and Ar-wave velocities, and atrial dimensions predicted HF in HFpEF but not HFrEF (all interaction p < 0.10). Prediction of HF readmission was not different in HFpEF and HFrEF (p = 0.93). Conclusions In this single-center echocardiographic study linked to Medicare claims, left ventricular dimensions and eccentric hypertrophy predicted HF readmission in HFrEF but not HFpEF and left ventricular wall thickness predicted HF readmission in HFpEF but not HFrEF. Regardless of LVEF, diastolic variables augmented prediction of HF readmission compared to echocardiographic structural variables, demographics, and comorbidities alone. The additional role of medication adherence, readmission history, and functional status in differential prediction of HF readmission by LVEF category should be considered for future study.

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Importance of structural heart disease and diastolic dysfunction in heart failure with preserved ejection fraction assessed according to the ESC guidelines - A substudy in the Ka (Karolinska) Ren (Rennes) study

Abstract: The majority of KaRen patients with suspected HFpEF had diagnostic echocardiographic criteria for HFpEF according to ESC Guidelines. Our findings support using 2016 ESC HF guidelines for risk prediction in HFpEF.

Cited by 13 publications

References 37 publications

Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients

Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients

Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction

Retrospective evaluation of echocardiographic variables for prediction of heart failure hospitalization in heart failure with preserved versus reduced ejection fraction: A single center experience

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