-
European Heart Journal Sep 2023To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and... (Meta-Analysis)
Meta-Analysis
AIMS
To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes.
METHODS AND RESULTS
A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR.
CONCLUSION
Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection.
Topics: Humans; Child; Adolescent; Aortic Valve; Heart Valve Prosthesis Implantation; Retrospective Studies; Prospective Studies; Heart Valve Prosthesis; Treatment Outcome
PubMed: 37366156
DOI: 10.1093/eurheartj/ehad370 -
Brazilian Journal of Cardiovascular... Oct 2023Aortic stenosis (AS) is the most common valvular heart disease and the most common indication for aortic valve replacement in adults. Aortic valve neocuspidization...
INTRODUCTION
Aortic stenosis (AS) is the most common valvular heart disease and the most common indication for aortic valve replacement in adults. Aortic valve neocuspidization (AVNeo) with fixed autologous pericardium, also known as the Ozaki procedure, is a possible alternative treatment of AS. Autopericardial valves save the dynamics and physiological anatomy of the aortic root, however, the service life of autopericardial leaflets is limited. There is no data about factors that may influence the development of AVNeo insufficiency. Here, we assessed the effect of autopericardial leaflet symmetry on the development of aortic insufficiency after Ozaki procedure.
METHODS
This study included 381 patients with AS who underwent Ozaki procedure. Patients were divided into group 1 (171 patients with symmetric aortic root) and group 2 (210 patients with asymmetric aortic root).
RESULTS
The maximum observation period was up to 65 months. Sixteen cases of aortic insufficiency were detected in group 1, and 33 cases were detected in group 2. Based on the results of Cox regression, the predictors of aortic insufficiency in the late postoperative period are age and asymmetry of neocusps. According to results of Kaplan-Meier analysis, insufficiency of AVNeo in the maximum follow-up period after surgical correction of AS for group 1 patients was significantly lower than for group 2 patients (P=0.006).
CONCLUSION
Asymmetric neocusps increase the risk of aortic insufficiency in the mid-term period after Ozaki procedure. And the older the patients at the time of surgery, the less likely they develop AVNeo insufficiency.
Topics: Adult; Humans; Aortic Valve; Heart Valve Diseases; Aortic Valve Stenosis; Aortic Valve Insufficiency; Heart Valve Prosthesis; Pericardium; Treatment Outcome
PubMed: 37797236
DOI: 10.21470/1678-9741-2022-0370 -
European Heart Journal Sep 2023The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock... (Observational Study)
Observational Study
AIMS
The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed.
METHODS AND RESULTS
CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality.
CONCLUSION
This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.
Topics: Humans; United States; Transcatheter Aortic Valve Replacement; Shock, Cardiogenic; Quality of Life; Aortic Valve Stenosis; Treatment Outcome; Aortic Valve; Registries; Risk Factors
PubMed: 37350747
DOI: 10.1093/eurheartj/ehad387 -
Revista Portuguesa de Cardiologia :... Aug 2023Nearly 300 years after the first description of aortic valve obstruction, it has taken less than two decades of randomized clinical trials (RCTs) for transcatheter... (Review)
Review
Nearly 300 years after the first description of aortic valve obstruction, it has taken less than two decades of randomized clinical trials (RCTs) for transcatheter aortic valve implantation (TAVI) to become a recognized strategy for patients with aortic stenosis. The high density of recent publications makes it easy to ignore the history that led to the development of this procedure. Knowing the evolution of a diagnostic or therapeutic technique improves critical reasoning, prevents repeated mistakes, paves the way for future research and contributes to an insightful perspective on the subject. Nevertheless, it should not overshadow the findings of recently published RCTs, which still are the mainstay of clinical practice. In this timeline review, the authors aim to recap the development of TAVI, combining the pathophysiology of aortic stenosis and the initial concept of TAVI with the roadmap of clinical trials that led to the generalization of the TAVI procedure.
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve; Aortic Valve Stenosis; Treatment Outcome
PubMed: 36948456
DOI: 10.1016/j.repc.2022.09.004 -
Biology of Sex Differences Jul 2023Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females...
BACKGROUND
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF.
METHODS
KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables.
RESULTS
Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010).
CONCLUSIONS
In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.
Topics: Humans; Female; Male; Aortic Valve; Heart Valve Diseases; Interleukin-6; Coronary Artery Disease; Renal Insufficiency, Chronic; Inflammation; Renal Insufficiency
PubMed: 37443048
DOI: 10.1186/s13293-023-00530-x -
European Journal of Cardio-thoracic... Sep 2023To support clinical decision-making in children with aortic valve disease, by compiling the available evidence on outcome after paediatric aortic valve repair (AVr). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To support clinical decision-making in children with aortic valve disease, by compiling the available evidence on outcome after paediatric aortic valve repair (AVr).
METHODS
A systematic review of literature reporting clinical outcome after paediatric AVr (mean age at surgery <18 years) published between 1 January 1990 and 23 December 2021 was conducted. Early event risks, late event rates and time-to-event data were pooled. A microsimulation model was employed to simulate the lives of individual children, infants and neonates following AVr.
RESULTS
Forty-one publications were included, encompassing 2 623 patients with 17 217 patient-years of follow-up (median follow-up: 7.3 years; range: 1.0-14.4 years). Pooled mean age during repair for aortic stenosis in children (<18 years), infants (<1 year) or neonates (<30 days) was 5.2 ± 3.9 years, 35 ± 137 days and 11 ± 6 days, respectively. Pooled early mortality after stenosis repair in children, infants and neonates, respectively, was 3.5% (95% confidence interval: 1.9-6.5%), 7.4% (4.2-13.0%) and 10.7% (6.8-16.9%). Pooled late reintervention rate after stenosis repair in children, infants and neonates, respectively, was 3.31%/year (1.66-6.63%/year), 6.84%/year (3.95-11.83%/year) and 6.32%/year (3.04-13.15%/year); endocarditis 0.07%/year (0.03-0.21%/year), 0.23%/year (0.07-0.71%/year) and 0.49%/year (0.18-1.29%/year); and valve thrombosis 0.05%/year (0.01-0.26%/year), 0.15%/year (0.04-0.53%/year) and 0.19%/year (0.05-0.77%/year). Microsimulation-based mean life expectancy in the first 20 years for children, infants and neonates with aortic stenosis, respectively, was 18.4 years (95% credible interval: 18.1-18.7 years; relative survival compared to the matched general population: 92.2%), 16.8 years (16.5-17.0 years; relative survival: 84.2%) and 15.9 years (14.8-17.0 years; relative survival: 80.1%). Microsimulation-based 20-year risk of reintervention in children, infants and neonates, respectively, was 75.2% (72.9-77.2%), 53.8% (51.9-55.7%) and 50.8% (47.0-57.6%).
CONCLUSIONS
Long-term outcomes after paediatric AVr for stenosis are satisfactory and dependent on age at surgery. Despite a high hazard of reintervention for valve dysfunction and slightly impaired survival relative to the general population, AVr is associated with low valve-related event occurrences and should be considered in children with aortic valve disease.
Topics: Infant, Newborn; Humans; Child; Infant; Adolescent; Aortic Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Constriction, Pathologic; Aortic Valve Stenosis; Treatment Outcome; Retrospective Studies; Reoperation
PubMed: 37584683
DOI: 10.1093/ejcts/ezad284 -
Internal Medicine (Tokyo, Japan) Sep 2023
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve; Aortic Valve Stenosis
PubMed: 36725033
DOI: 10.2169/internalmedicine.1416-22 -
Journal of the American Heart... Aug 2023Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to... (Clinical Trial)
Clinical Trial
Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; =0.001), male sex (82.4% versus 57.7%; =0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; =0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; <0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; <0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m; <0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; <0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; =0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. Conclusions Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.
Topics: Aged; Humans; Male; Amyloidosis; Aortic Valve; Aortic Valve Stenosis; Cardiomyopathies; Prealbumin; Prospective Studies; Stroke; Stroke Volume; Technetium; Tomography, X-Ray Computed; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left
PubMed: 37581394
DOI: 10.1161/JAHA.123.030271 -
Nature Communications Jan 2024Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug...
Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.
Topics: Mice; Animals; Aortic Valve; Aortic Valve Stenosis; Osteogenesis; Calcinosis; Cells, Cultured; Magnetic Phenomena
PubMed: 38228638
DOI: 10.1038/s41467-024-44726-0 -
Advanced Science (Weinheim,... May 2024The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise...
The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.
Topics: Animals; Aortic Valve; Mice; Cellular Senescence; NF-E2-Related Factor 2; Calcinosis; Signal Transduction; Aortic Valve Stenosis; Disease Models, Animal; Cyclin D1; Male; Transcription Factors; Osteogenesis; Humans; Mice, Inbred C57BL
PubMed: 38502885
DOI: 10.1002/advs.202307319