Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis.
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SUBMITTER: White M
PROVIDER: S-EPMC8163007 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Detecting among patients with aortic stenosis (AS) those who are likely to rapidly progress, yet potentially benefiting from prophylactic aortic valve replacement, is needed for improved patient care. The objective of this study was to evaluate the role of imaging biomarkers in predicting the progression to clinical symptoms and death in patients with AS. Methods: We searched the Pubmed and the International Clinical Trials Registry Platform databases for studies including patients with AS, and investigating imaging techniques, published in any language until Jan 1, 2018. Eligible sets of data include effect of imaging biomarkers relative to: (1) Overall mortality, (2) Cardiac mortality, and (3) Overall events (Symptom onset and Major Adverse Cardiovascular Events). Meta-analysis was used to examine associations between the imaging biomarkers and outcomes of AS using Random Effect models. Results: Eight studies and 1,639 patients were included after systematic review. Four studies investigated aortic valve calcification (AVC) whereas the remaining investigated biomarkers provided by cardiac magnetic resonance (CMR). Four articles investigated the presence of midwall fibrosis on late-gadolinium enhancement imaging, three reported its extent (LGE%) and two, the myocardial extracellular volume (ECV). By decreasing strength of association, there were significant associations between cardiac mortality and LGE% [Relative Risk (RR) = 1.05, 95% Confidence Interval (CI) 1.01-1.10]; overall mortality and AVC (RR = 1.19, 95%CI: 1.05-1.36); overall events and ECV (RR = 1.68, 95%CI: 1.17-2.41); cardiac mortality and midwall fibrosis (RR = 2.88, 95%CI: 1.12-7.39). Conclusion: AVC and myocardial fibrosis imaging biomarkers predict the outcomes in AS, and help understanding AS pathophysiology and setting therapeutic targets.
| S-EPMC6113371 | biostudies-literature
Project description: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.
| S-EPMC9109115 | biostudies-literature
Project description:AimsAortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients.Methods and resultsWe performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I2 = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I2 = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone.ConclusionsTAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.
| S-EPMC9715797 | biostudies-literature
Project description:BackgroundAortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled the patient's condition will be. Therefore, timely and accurate diagnosis is significant for AD. Blood biomarker testing as a method of liquid biopsy can improve the diagnostic efficiency of AD. This study conducted a systematic review of the current blood diagnostic biomarkers of AD.MethodsThe PubMed, Cochrane Library, Web of Science, and Embase electronic databases were systematically searched from inception to January 1, 2023, using the terms "aortic dissection", "serum", "plasma" and "diagnosis". Stata 12.0 software was used to perform Random effects meta-analysis was performed using Stata 12.0 software to determine the effect sizes and corresponding 95% confidence intervals. Then, a summary receiver operator characteristic (SROC) curve was drawn, and the area under the ROC curve (AUC) was calculated.ResultsD-dimer had the best sensitivity and AUC for AD, with values of 0.96 (95% CI: 0.93-0.98) and 0.95 (95% CI: 0.93-0.97), respectively. The sensitivity and AUC values for D-dimer with a cut-off value of 500 ng/mL were 0.97 (95% CI: 0.95-0.99) and 0.94 (95% CI: 0.92-0.96), respectively. In contrast, microRNA had a better specificity value for AD, at 0.79 (95% CI: 0.73-0.83).ConclusionsD-dimer and microRNA have good accuracy in the diagnosis of AD, but the specificity of D-dimer is worse, and studies of microRNA are insufficient. The combination of different biomarkers can improve the diagnostic accuracy. Other blood biomarkers are related to the pathological progression of AD and can be selected according to pathological progress.
| S-EPMC10563263 | biostudies-literature
Project description:Reverse left ventricular (LV) remodeling after aortic valve replacement (AVR), in patients with aortic stenosis, is well-documented as an important prognostic factor. With this systematic review and meta-analysis, we aimed to characterize the response of the unloaded LV after AVR. We searched on MEDLINE/PubMed and Web of Science for studies reporting echocardiographic findings before and at least 1 month after AVR for the treatment of aortic stenosis. In total, 1,836 studies were identified and 1,098 were screened for inclusion. The main factors of interest were structural and dynamic measures of the LV and aortic valve. We performed a random-effects meta-analysis to compute standardized mean differences (SMD) between follow-up and baseline values for each outcome. Twenty-seven studies met the eligibility criteria, yielding 11,751 patients. AVR resulted in reduced mean aortic gradient (SMD: -38.23 mmHg, 95% CI: -39.88 to -36.58 , I2=92% ), LV mass (SMD: -37.24 g, 95% CI: -49.31 to -25.18 , I2=96% ), end-diastolic LV diameter (SMD: -1.78 mm, 95% CI: -2.80 to -0.76 , I2=96% ), end-diastolic LV volume (SMD: -1.6 ml, 95% CI: -6.68 to 3.51, I2=91% ), increased effective aortic valve area (SMD: 1.10 cm2, 95% CI: 1.01 to 1.20, I2=98% ), and LV ejection fraction (SMD: 2.35%, 95% CI: 1.31 to 3.40%, I2=94.1% ). Our results characterize the extent to which reverse remodeling is expected to occur after AVR. Notably, in our study, reverse remodeling was documented as soon as 1 month after AVR.
| S-EPMC11254856 | biostudies-literature
Project description:BackgroundHypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes.ObjectiveTo assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS.DesignSystematic review and meta-analysis.Data sourcesThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019.Study eligibility criteria, appraisal and synthesis methodsTwo independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R.Main outcome measuresMortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fraction RESULTS: From 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin-angiotensin-aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance.ConclusionAHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.
| S-EPMC7537451 | biostudies-literature
Project description:Symptomatic aortic stenosis has a poor prognosis. Many patients are considered inoperable or at high surgical risk for surgical aortic valve replacement (SAVR), reflecting their age, comorbidities and frailty. The clinical effectiveness and safety of TAVI have not been reviewed systematically for these high levels of surgical risk. This systematic review compares mortality and other important clinical outcomes up to 5 years post treatment following TAVI or other treatment in these risk groups.A systematic review protocol was registered on the PROSPERO database (CRD42016048396). The Cochrane Library, Centre for Reviews and Dissemination Databases, MEDLINE, EMBASE, and ZETOC were searched from January 2002 to August 2016. Clinical trials or matched studies comparing TAVI with other treatments for AS in patients surgically inoperable or operable at a high risk were included. Data extraction and quality assessment were conducted by two reviewers. Data were pooled using random-effects meta-analysis. The main outcomes were all-cause mortality, efficacy and major complications.Three good quality randomised controlled trials (RCTs) were included. Patients' mean age ranged from 83-85 years, around half were female and New York Heart Association (NYHA) functional class III or IV ranged from 83.8% to 94.2% with frequent comorbidities. In 358 surgically inoperable patients from one RCT, TAVI was superior to medical therapy for all-cause mortality at 1 year (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.36-0.92), 2 years (HR 0.50, 95% CI 0.39-0.65), 3 years (HR 0.53, 95% CI 0.41to 0.68) and 5 years (HR 0.50, 95% CI 0.39-0.65), and NYHA class III or IV at 2 years (TAVI 16.8% (16/95), medical therapy 57.5% (23/40), p<0.001), quality of life and re-hospitalisation. TAVI had higher risks of major bleeding up to 1 year, of stroke up to 3 years (at one year 11.2% versus 5.5%, p = .06; HR at 2 years 2.79, 95% CI 1.25-6.22; HR at 3 years 2.81; 95% CI 1.26-6.26) and of major vascular complication at 3 years (HR 8.27, 95% CI 2.92-23.44). Using the GRADE tool, this evidence was considered to be of moderate quality. In a meta-analysis including 1,494 high risk surgically operable patients from two non-inferiority RCTs TAVI showed no significant differences from SAVR in all-cause mortality at two years (HR 1.03, 95% CI 0.82-1.29) and up to 5 years (HR 0.83, 95% CI 0.83-1.12). There were no statistically significant differences in major vascular complications and myocardial infarction at any time point, discrepant results for major bleeding on variable definitions and no differences in stroke rate at any time point. Using the GRADE tool, this evidence was considered of low quality.Symptomatic aortic stenosis can be lethal without intervention but surgical resection is contraindicated for some patients and high risk for others. We found that all-cause mortality up to 5 years of follow-up did not differ significantly between TAVI and SAVR in patients surgically operable at a high risk, but favoured TAVI over medical therapy in patients surgically inoperable. TAVI is a viable life-extending treatment option in these surgical high risk groups.
| S-EPMC5944928 | biostudies-literature
Project description:BackgroundPatients with obstruction to the left ventricular outflow tract from degenerative aortic stenosis (AS) usually do not become symptomatic until their disease becomes graded as severe. We sought to assess the accuracy of the physical examination for the diagnosis of AS of at least moderate severity.MethodsA systematic review and meta-analysis of case series and cohorts of patients who received a cardiovascular physical examination prior to receiving a left heart catheterization or an echocardiogram. PubMed, Ovid MEDLINE, the Cochrane Library, ClinicalTrials.gov, and Embase were searched with a date range from inception through December 10, 2021, without language restrictions.ResultsOur systematic review yielded 7 observational studies with adequate data to perform a meta-analysis on 3 physical examination assessments. Auscultating a diminished second heart sound (likelihood ratio [LR] = 10.87, 95% confidence interval [CI], 3.94-30.12, P < 0.05) and palpating a delayed carotid upstroke (LR = 9.04, 95% CI, 3.12-25.44, P < 0.05) are useful for detecting AS of at least moderate severity. The absence of a systolic murmur radiating to the neck (LR = 0.11, 95% CI, 0.06-0.23, P < 0.05) rules against AS of at least moderate severity.ConclusionsLow-quality evidence from observational studies supports a diminished second heart sound and a delayed carotid upstroke as having moderate accuracy in diagnosing the presence of AS of at least moderate severity, whereas the absence of a murmur radiating to the neck is equally accurate in excluding this diagnosis.
| S-EPMC10290951 | biostudies-literature
Project description:Background:Patients with severe aortic stenosis and concomitant active cancer (AC) are considered high-risk patients and usually are not allowed to undergo surgical valve replacement. Transcatheter aortic valve replacement (TAVR) may be an attractive option for them; however, little is known about the outcomes of TAVR in this subset of complex patients. Methods and results:In this meta-analysis, Medline, Cochrane Library and Scopus databases were searched (anytime up to April 2019) for studies evaluating the outcomes of TAVR in patients with or without AC. We assessed pooled estimates (with their 95% CIs) of the risk ratio (RR) for the all-cause mortality at the 30-day and 1-year follow-ups, a 4-point safety outcome (any bleeding, stroke, need for a pacemaker and acute kidney injury) and a 2-point efficacy outcome (device success and residual mean gradient (mean difference)). Three studies (5162 patients) were included. Of those patients, a total of 368 (7.1%) had AC. Apart from a significantly higher need for a postprocedural pacemaker (RR 1.29, 95%?CI 1.06 to 1.58, p=0.01), TAVR in patients with AC resulted in similar outcomes for safety and efficacy at the 30-day follow-up compared with those without AC. Patients with AC experienced similar rates of the all-cause mortality at the 30-day follow-up compared with those without (RR 0.92, 95%?CI 0.53 to 1.59, p=0.76); however, the all-cause mortality was significantly higher in patients with AC at the 1-year follow-up (RR 1.71, 95%?CI 1.26 to 2.33, p=0.0006). This mortality difference was independent of cancer stage (advanced or limited) at the 30-day follow-up but not at the 1-year follow-up; only patients with limited cancer stages showed similar all-cause mortality rates compared with those without cancer at the 1-year follow-up (RR 1.22, 95%?CI 0.79 to 1.91, p=0.37). Conclusion:TAVR in patients with AC is associated with similar 30-day and potentially worse 1-year outcomes compared with those in patients without AC. The 1-year all-cause mortality appears to be dependent on the cancer stage. Involving a specialised oncologist who usually considers cancer stage in the decision-making process and applying additional preoperative scores such as frailty indices might refine the risk assessment process among these patients. PROSPERO registration number:CRD42019120416.
| S-EPMC7066604 | biostudies-literature
Project description:The survival benefits of aortic valve replacement (AVR) in the different flow-gradient states of severe aortic stenosis (AS) is not known. A comprehensive search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were conducted to identify studies that investigated the prognosis of severe AS (effective orifice area ≤1.0 cm2) and left ventricular ejection fraction ≥50%. Severe AS was stratified by mean pressure gradient [threshold of 40 mmHg; high-gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35 ml/m2; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted to assess all-cause mortality among each AS sub-type with rate ratio (RR) reported. The effects of AVR on prognosis were examined using network meta-regression. In the pooled analysis (15 studies and 9,737 patients), LF states (both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88; 95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS; and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR 1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred different survival benefits: it was most effective in NFHG (RR with AVR /RR without AVR : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR with AVR /RR without AVR : 1.19; 95% CI: 0.74-1.94).
| S-EPMC5505951 | biostudies-literature