Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

White, Maddie; Baral, Ranu; Ryding, Alisdair; Tsampasian, Vasiliki; Ravindrarajah, Thuwarahan; Garg, Pankaj; Koskinas, Konstantinos C.; Clark, Allan; Vassiliou, Vassilios

doi:10.3390/medsci9020029

Cited by 16 publications

(33 citation statements)

References 81 publications

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“…Nevertheless, in the era of personalised medicine, the identification of the high-risk population and the decision regarding intervention should be made after careful individual risk assessment and evaluation not only of symptoms but also of indirect signs of myocardial decompensation and damage that could have a negative impact on the prognosis and outcome. Such parameters could include the presence of mid-wall late gadolinium enhancement of cardiovascular magnetic resonance, utilisation of left ventricular stroke volume in preference to LVEF or various biomarkers (eg, N-terminal pro b-type natriuretic peptide/BNP, high-sensitivity troponin), which are associated with a worse outcome 32–35. These clues could help refine the optimal timing of intervention for each patient 35–37.…”

Section: Discussionmentioning

confidence: 99%

“…Such parameters could include the presence of mid-wall late gadolinium enhancement of cardiovascular magnetic resonance, utilisation of left ventricular stroke volume in preference to LVEF or various biomarkers (eg, N-terminal pro b-type natriuretic peptide/BNP, high-sensitivity troponin), which are associated with a worse outcome 32–35. These clues could help refine the optimal timing of intervention for each patient 35–37. The results of currently ongoing randomised trials investigating these parameters are greatly anticipated to help clarify the role of these parameters in the risk assessment of patients with severe aortic stenosis and the impact of early intervention on the outcome and prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

et al. 2022

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ObjectivesThe management of severe aortic stenosis mandates consideration of aortic valve intervention for symptomatic patients. However, for asymptomatic patients with severe aortic stenosis, recent randomised trials supported earlier intervention. We conducted a systematic review and meta-analysis to evaluate all the available data comparing the two management strategies.MethodsPubMed, Cochrane and Web of Science databases were systematically searched from inception until 10 January 2022. The search key terms were ‘asymptomatic’, ‘severe aortic stenosis’ and ‘intervention’.ResultsMeta-analysis of two published randomised trials, AVATAR and RECOVERY, included 302 patients and showed that early intervention resulted in 55% reduction in all-cause mortality (HR=0.45, 95% CI 0.24 to 0.86; I2 0%) and 79% reduction in risk of hospitalisation for heart failure (HR=0.21, 95% CI 0.05 to 0.96; I2 15%). There was no difference in risk of cardiovascular death between the two groups (HR=0.36, 95% CI 0.03 to 3.78; I2 78%). Additionally, meta-analysis of eight observational studies showed improved mortality in patients treated with early intervention (HR=0.38, 95% CI 0.26 to 0.56; I2 77%).ConclusionThis meta-analysis provides evidence that, in patients with severe asymptomatic aortic stenosis, early intervention reduces all-cause mortality and improves outcomes compared with conservative management. While this is very encouraging, further randomised controlled studies are needed to draw firm conclusions and identify the optimal timing of intervention.PROSPERO registration numberCRD42022301037.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

et al. 2022

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“…Several types of biomarkers have been studied in aortic valve stenosis patients, including cardiac troponins and natriuretic peptides, and have been shown to correlate with patient mortality (13). A major interest of biomarker studies in aortic valve stenosis, apart from evaluating prognosis, would be to guide the ideal time frame for valve intervention, a topic possibly to be explored in clinical trials, in the case of ALP.…”

Section: Discussionmentioning

confidence: 99%

Plasma alkaline phosphatase is associated to mortality risk in aortic valve stenosis patients

Nunes

2022

Preprint

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Background: aortic valve stenosis is an important clinical condition, with a significant mortality rate in the elderly. Plasma values of alkaline phosphatase (ALP) have been shown to act as a marker of prognosis in different clinical conditions and in the general population. Methods: Plasma levels of alkaline phosphatase were studied in a cohort of patients with aortic valve stenosis, and a five-year survival evaluation was carried out. Results: 24 patients were under study, of which 12 were dead at 5-year follow-up. The median age at baseline evaluation was 79 years (interquartile range, 72-85 years), and 11 patients were of the female sex (13 were male). The median value of ALP, of 83 IU/L, was used to separate patients into two groups; 2 patients died in the group with low ALP values versus 10 patients who died in the group with high ALP values. Using ALP with the same cut-off level, Kaplan Meyer study with log-rank analysis showed a significance level <0.01. Cox regression analysis showed an overall significant result, with a significant level for plasma ALP (significance level 0.03), but not for age, sex or transvalvular gradient (assessed by echocardiography). Conclusions: Elevated plasma ALP is associated to increased mortality risk in aortic valve stenosis patients. This finding may merit evaluation in studies with a larger number of patients.

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“…Positron emission tomography in patients with isolated AS can detect aortic valve inflammation and microcalcifications, which are associated with faster progression, and could be used to identify a high-risk mixed AS/AR group 32. Similarly, brain natriuretic peptide provides valuable prognostic information in asymptomatic patients with isolated severe AS and can be used in mixed AS/AR population 33. Other biomarkers shown to predict outcomes in AS, such as troponin and galectin-3, also hold promise in mixed AS/AR 33…”

Section: Diagnosis and Quantificationmentioning

confidence: 99%

“…Similarly, brain natriuretic peptide provides valuable prognostic information in asymptomatic patients with isolated severe AS and can be used in mixed AS/AR population 33. Other biomarkers shown to predict outcomes in AS, such as troponin and galectin-3, also hold promise in mixed AS/AR 33…”

Section: Diagnosis and Quantificationmentioning

confidence: 99%

Mixed aortic stenosis and regurgitation: a clinical conundrum

Nedadur

Belzile

Farrell

et al. 2022

Heart

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Mixed aortic stenosis (AS) and aortic regurgitation (AR) is the most frequent concomitant valve disease worldwide and represents a heterogeneous population ranging from mild AS with severe AR to mild AR with severe AS. About 6.8% of patients with at least moderate AS will also have moderate or greater AR, and 17.9% of patients with at least moderate AR will suffer from moderate or greater AS. Interest in mixed AS/AR has increased, with studies demonstrating that patients with moderate mixed AS/AR have similar outcomes to those with isolated severe AS. The diagnosis and quantification of mixed AS/AR severity are predominantly echocardiography-based, but the combined lesions lead to significant limitations in the assessment. Aortic valve peak velocity is the best parameter to evaluate the combined haemodynamic impact of both lesions, with a peak velocity greater than 4.0 m/s suggesting severe mixed AS/AR. Moreover, symptoms, increased left ventricular wall thickness and filling pressures, and abnormal left ventricular global longitudinal strain likely identify high-risk patients who may benefit from closer follow-up. Although guidelines recommend interventions based on the predominant lesion, some patients could potentially benefit from earlier intervention. Once a patient is deemed to require intervention, for patients receiving transcatheter valves, the presence of mixed AS/AR could confer benefit to those at high risk of paravalvular leak. Overall, the current approach of managing patients based on the dominant lesion might be too reductionist and a more holistic approach including biomarkers and multimodality imaging cardiac remodelling and inflammation data might be more appropriate.

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Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis

Cited by 16 publications

References 81 publications

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

Plasma alkaline phosphatase is associated to mortality risk in aortic valve stenosis patients

Mixed aortic stenosis and regurgitation: a clinical conundrum

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