Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis.

Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the condition's mechanistic underpinning has shifted the paradigm to an active disease process. This advancement from the 'wear and tear' model is a result of the growing economic and health burden of AS, particularly within industrialised countries, prompting further research. The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options.There is an unmet clinical need for asymptomatic patient management; no pharmacotherapies are proven to slow progression and intervention timing varies. Novel approaches are developing to address this through: (1) screening with circulating biomarkers; (2) development of drugs to slow disease progression and (3) early valve intervention guided by medical imaging. Existing biomarkers (troponin and brain natriuretic peptide) are non-specific, but cost-effective predictors of ventricular dysfunction. In addition, their integration with cardiovascular MRI can provide accurate risk stratification, aiding aortic valve replacement decision making. Currently, invasive intervention is the only treatment for AS. In comparison, the development of lipoprotein(a) lowering therapies could provide an alternative; slowing progression of CAS, preventing left ventricular dysfunction and reducing reliance on surgical intervention.The landscape of AS management is rapidly evolving. This review outlines current understanding of the pathophysiology of AS, its management and future perspectives for the condition's assessment and treatment.

Transcatheter aortic valve implantation in patients with severe symptomatic aortic valve stenosis: systematic review of cost-effectiveness analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a less invasive and costly treatment for patients with severe aortic stenosis (AS). This study aimed to systematically review the published literature focusing on economic evaluation of TAVI compared with other alternative treatments in AS populations. METHODS: A systematic review was conducted from inception until May 2021 using PubMed, Scopus, Web of science and Embase databases. The qualities of included studies were evaluated using Consolidated Health Economic Evaluation Reporting Standard (CHEERS) criteria. Data of costs, outcomes, incremental cost-effectiveness ratio (ICER) and willingness to pay were extracted. To compare results, ICERs were converted to the 2020 United States dollar (USD) rate. RESULTS: Of the 29 included cost-effectiveness studies, TAVI was cost-effective in all studies in the low-risk group (3/3), 77% of studies (7/9) in the intermediate-risk group, half of the studies (6/12) in the high-risk group, and 83% of studies (10/12) in the inoperable group. When adjusted to USD 2020, ICERs ranged from USD 2741 to 1027,674 USD per quality-adjusted life-year gained. The overall quality of the studies ranged from moderate to high. CONCLUSIONS: TAVI is potentially a cost-effective alternative to surgical aortic valve replacement (SAVR) for patients with operable AS with low, intermediate or high risk compared with medical management (MM) for patients with inoperable AS. TAVI was associated with a significant gain in quality-adjusted life-years in almost all studies compared to either SAVR or MM. TAVI is a costly procedure; therefore, justifying its cost-effectiveness depends on the acceptable threshold in each country.

Eficacia y seguridad del dispositivo de prótesis valvular aórtico percutáneo para estenosis aórtica severa / Efficacy and Safety of Percutaneous Aortic Valve Prosthesis Device for Severe Aortic Stenosis

INTRODUCCIÓN: La Estenosis Aórtica (EA) es la valvulopatía más frecuente en el mundo, cuya incidencia se va incrementando con el envejecimiento de la población; su etiología se asocia a la calcificación de la válvula con una prevalencia del 50%-70% en pacientes de la tercera edad; que por lo general son individuos que poseían una válvula aórtica anatómicamente normal que desarrolla calcificación entre la sexta y séptima década de la vida. La estenosis aórtica severa es una condición que afecta a las personas en edad avanzada, consiste en la obstrucción del flujo sanguíneo a través de la válvula aórtica debido a la fibrosis y calcificación de la misma, comprendida como un área de la válvula aórtica (AVA) 40 mm Hg y/o una velocidad máxima del chorro aórtico (Vmax) >4 m/s. Un 30% del total de pacientes que padecen estenosis aórtica severa tienen riesgo quirúrgico muy elevado para cirugía convencional. Entre ellos figuran los pacientes de edad avanzada, a quienes se les debe evitar este tipo de cirugía, así como la circulación extracorpórea. Uno de los tratamientos más recientes para esta condición médica es el reemplazo percutáneo de la válvula aórtica o reemplazo transcatéter de la válvula aórtica. El Implante o reemplazo transcatéter de válvula aórtica, es una técnica en la que se puede implantar una válvula aórtica artificial guiada a través de un catéter introducido por punción de una arteria (femoral, axilar, aorta) o por la punta del corazón (vía apical). Todo ello sin parar el corazón ni necesitar seccionar de forma completa el esternón (como en la cirugía convencional) ni usar circulación extracorpórea El objetivo de la presente Evaluación de tecnología sanitaria (ETS) es evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura con el del dispositivo prótesis valvular aórtico percutáneo o transcatéter de válvula aórtica en el tratamiento de pacientes con estenosis aórtica severa y con elevado riesgo quirúrgico o inoperables por cirugía convencional. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE, hasta el 11 de mayo de 2022. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales agencias de tecnologías sanitarias y guías de práctica clínica. RESULTADOS: Se identificaron 9 Revisiones sistemáticas (RS), 4 Evaluación de Tecnologías Sanitarias (ETS) y una evaluación económica (EC) realizada para Chile. No se identificaron EC para Perú, ni Guías de Práctica Clínica (GPC) que puedan responder la pregunta PICO. La más reciente revisión sistemática del año 2021, incorpora la evidencia actualizada de los dos grandes ensayos clínicos que responden la pregunta, mientras que las demás RS incluyen parte de estos ensayos. La evaluación de la calidad de la RS más reciente ha sido valorada como baja debido a que solo presenta un criterio crítico. CONCLUSIONES: La evidencia identificada en relación al implante valvular aórtico percutáneo para estenosis aórtica severa en pacientes con elevado riesgo quirúrgico, encontró que no se encuentran diferencias estadísticamente significativas entre ambos grupos en los desenlaces de: mortalidad por todas las causas, mortalidad por causa cardiovascular, stroke, stroke mayor discapacitante, infarto de miocardio, endocarditis, reintervención o reparación, hasta luego de 5 años de seguimiento. Se observó un menor riesgo para TAVI comparado con SAVR para los desenlaces: sangrado mayor, nuevo inicio o empeoramiento de fibrilación auricular. Por otro lado, se observó un mayor riesgo con TAVI comparado con SAVR para complicaciones vasculares mayores e implantación de marcapasos permanente.

Drugs for Prevention and Treatment of Aortic Stenosis: How Close Are We?

Aortic stenosis is one of the most common cardiovascular diseases in the world. Extensive work on the underlying pathophysiology responsible for calcific aortic valve disease and its progression to aortic stenosis has described a complex process involving inflammation, lipid deposition, mineralisation, and genetic factors such as elevated lipoprotein(a). With the advancement of gene silencing technology and development of novel therapeutic agents, we may now be closer than ever to having medical therapies that prevent, or at least slow the progression of aortic stenosis. In this review, we highlight the pathophysiology and risk factors of calcific aortic valve disease, along with current, potential, and emerging novel medical therapies. We also provide potential explanations for the failure of statin trials and suggest new avenues for research and new randomised trials in this area.

Coronary Microcirculation in Aortic Stenosis: Pathophysiology, Invasive Assessment, and Future Directions.

With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and define severity. A better understanding of the microvasculature in AS could improve clinical care by predicting left ventricular remodeling or anticipate the interplay between epicardial stenosis and myocardial dysfunction. In this review, we combine five decades of literature regarding microvascular, coronary, and aortic valve physiology with emerging insights from newly developed invasive tools for quantifying microcirculatory function. Furthermore, we describe the coupling between microcirculation and epicardial stenosis, which is currently under investigation in several randomized trials enrolling subjects with concomitant AS and coronary disease. To clarify the physiology explained previously, we present two instructive cases with invasive pressure measurements quantifying coexisting valve and coronary stenoses. Finally, we pose open clinical and research questions whose answers would further expand our knowledge of microvascular dysfunction in AS. These trials were registered with NCT03042104, NCT03094143, and NCT02436655.

Management of Aortic Stenosis in Patients With End-Stage Renal Disease on Hemodialysis.

BACKGROUND: Patients with end-stage renal disease on hemodialysis (ESRD-HD) and aortic stenosis have poor prognosis. The role of transcatheter aortic valve replacement (TAVR) in this high-risk population is debated. METHODS: We compared the outcomes among ESRD-HD Medicare beneficiaries who were managed with TAVR, surgical AVR (SAVR), or conservative management for aortic stenosis between 2015 and 2017, using overlap propensity score weighting analysis to control for differences in treatment assignment. The primary outcome was all-cause mortality and was compared between treatment groups as well as to age-sex matched mortality for ESRD-HD in the US population. Secondary outcomes included trend of heart failure hospitalizations. RESULTS: A total of 8107 ESRD-HD patients with aortic stenosis were included, 4130 (50%) underwent TAVR, 2565 (31.6%) underwent SAVR, and 1412 (17.4%) were managed conservatively. TAVR patients had more comorbidities and higher frailty compared with the other 2 groups. Thirty-day mortality was lower with TAVR compared with SAVR (4.6% versus 12.8%, P<0.01). After a median follow-up of 465 days (interquartile range, 261-759), on overlap propensity score weighting analysis, there was no difference in mortality between TAVR and SAVR (adjusted hazard ratio, 1.02 [95% CI, 0.91-1.15], P=0.7), and mortality was lower with TAVR compared with conservative management (adjusted hazard ratio, 0.53 [95% CI, 0.47-0.60], P<0.001). Standardized mortality ratios with TAVR, SAVR, and conservative management compared with age-sex matched ESRD-HD US population were 1.24, 1.27, and 1.83, respectively. The rate of heart failure admissions declined after TAVR (incidence rate ratio, 0.55 [95% CI, 0.48-0.62], P<0.001) and SAVR (incidence rate ratio, 0.76 [95% CI, 0.65-0.88], P<0.001). CONCLUSIONS: In ESRD-HD patients with aortic stenosis, mortality was lower in the short-term with TAVR compared with SAVR but comparable in the mid-term. AVR is associated with an improvement in survival and reduction in heart failure hospitalizations compared with conservative management.

Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: A Decision Analysis.

BACKGROUND: Fetal aortic valvuloplasty (FAV) may prevent progression of midgestation aortic stenosis to hypoplastic left heart syndrome. However, FAV has well-established risks, and its survival benefit remains unknown. Our primary aim was to determine whether FAV for midgestation aortic stenosis increases survival from fetal diagnosis to age 6 years. METHODS AND RESULTS: We performed a retrospective analysis of 143 fetuses who underwent FAV from 2000 to 2017 and a secondary analysis of the Pediatric Heart Network Single Ventricle Reconstruction trial. Using these results, we developed a decision model to estimate probability of transplant-free survival from fetal diagnosis to age 6 years and postnatal restricted mean transplant-free survival time. FAV was technically successful in 84% of 143 fetuses with fetal demise in 8%. Biventricular circulation was achieved in 50% of 111 live-born infants with successful FAV but in only 16% of the 19 patients with unsuccessful FAV. The model projected overlapping probabilities of transplant-free survival to age 6 years at 75% (95% CI, 67%-82%) with FAV versus 72% (95% CI, 61%-82%) with expectant fetal management, resulting in a restricted mean transplant-free survival time benefit of 1.2 months. When limiting analyses to the improved FAV experience since 2009 to reflect current practice, (probability of technical success [94%], fetal demise [4%], and biventricular circulation [66%]), the model projected that FAV increased the probability of survival to age 6 years to 82% (95% CI, 73%-89%). Expectant management is favored if risk of fetal demise exceeded 12% or probability of biventricular circulation fell below 26%, but FAV remained favored over plausible recent range of technical success. CONCLUSIONS: Our model suggests that FAV provides a modest, medium-term survival benefit over expectant fetal management. Appropriate patient selection and low risk of fetal demise with FAV are critical factors for obtaining a survival benefit.

Aortic stenosis in women.

Aortic stenosis (AS) is a common valve disorder in an ageing population in western countries, and women, with longer life expectancy, comprise a substantial percentage of elderly patients with AS. Compared with men, women exhibit distinctive characteristics at the level of stenotic valve leaflets and subsequent compensatory responses of the left ventricle to chronic pressure overload, and in clinical presentation, consequences and response to intervention. Randomised controlled trials of transcatheter aortic valve implantation have yielded new evidence of sex differences in both short-term and long-term outcomes after intervention. A comprehensive knowledge of the existing evidence may inform our understanding of gender differences during assessment and treatment of patients with AS. In this paper, we review the available evidence regarding sex differences in AS in terms of symptoms, clinical presentation, anatomical differences and pathophysiological progression, management and outcomes after aortic valve replacement. Implications for further research are suggested.

Assessment of the prognostic significance of low gradient severe aortic stenosis and preserved left ventricular function requires the integration of the consistency of stroke volume calculation and clinical data.

BACKGROUND: This study was to evaluate the prognostic significance of low gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF) with the integration of echocardiographic and clinical data. METHODS: The study included 172 patients with LG SAS (AVAi ≤ 0.6 cm2 /m2 , mean aortic pressure gradient < 40 mm Hg) and LVEF (≥ 50%). LV outflow tract diameters were measured at both the aortic valve annulus and 5 mm below the annulus for the measurement consistency. Patients were divided into the low flow LG SAS (LF/LG SAS: SVi < 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ) and normal-flow LG SAS groups (NF/LG SAS: SVi ≥ 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ). Echocardiographic findings and clinical data were systematically analyzed with mean follow-up of 3.0 ± 1.6 years. RESULTS: LF/LG SAS had significantly smaller AVAi, lower SVi, a higher prevalence of atrial fibrillation (28% vs 12% P = .01) and diabetes (47% vs 27% P = .007) and lower 3-year cumulative survival than NF/LG SAS. Multivariable analysis showed that dyspnea, renal dysfunction (CI 1.42-3.99, P < .01), left atrial diameter, and SVi were independently associated with an increased risk for all-cause mortality. Aortic valve intervention (AVI) improved survival in LF/LG SAS (68% vs 48%, P < .05) in comparison with medical management (HR: 4.20, CI: 1.12-15.76, P = .03), but only modestly in NF/LG SAS (75% vs 65% P > .05). CONCLUSION: Outcome of LG SAS was independently associated with clinical characteristics. AVI likely improved outcome of LF/LG SAS who had high-risk clinical characteristics and unfavorable echocardiographic findings.

Aortic Valve Stenosis Treatment Disparities in the Underserved: JACC Council Perspectives.

Underserved minorities make up a disproportionately small subset of patients in the United States undergoing transcatheter and surgical aortic valve replacement for aortic stenosis. The reasons for these treatment gaps include differences in disease prevalence and patient, health care system, and disease-related factors. This has major implications not only for minority patients, but also for other groups who face similar challenges in accessing state-of-the-art care for structural heart disease. The authors propose the following key strategies to address these treatment disparities: 1) implementation of measure-based quality improvement programs; 2) effective culturally competent communication and team-based care; 3) improving patient health care access, education, and effective diagnosis; and 4) changing the research paradigm that creates an innovation pipeline for patients. Only a concerted effort from all stakeholders will achieve equitable and broad application of this and other novel structural heart disease treatment modalities in the future.

Clinical practice guideline for the evaluation and management of patients with severe aortic stenosis for the Peruvian Social Security.

Introduction: This article summarizes the clinical practice guide (CPG) for the evaluation and management of patients with severe aortic stenosis in the Social Security of Peru (EsSalud). Objective: To provide clinical evidence-based recommendations for the evaluation and management of patients with severe aortic stenosis in the EsSalud. Methods: A local guideline development group (local GDG) was established, including medical specialists and methodologists. The local GDG formulated 7 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and, when it was considered pertinent, primary studies, were conducted in PubMed during 2018. The evidence to answer each of the posed clinical questions was selected. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice, and the flowchart of evaluation and management. Finally, the CPG was approved with Resolution N.° 47 - IETSI - ESSALUD - 2018. Results: This CPG addressed 7 clinical questions regarding two issues: the initial evaluation and the management of severe aortic stenosis. Based on these questions, 9 recommendations (1 strong recommendation and 8 weak recommendations), 16 points of good clinical practice, and 1 flowchart were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions from the CPG for the evaluation and management of patients with severe aortic stenosis in the EsSalud.

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud basadas en evidencia científica. Métodos: Se conformó un grupo elaborador local (GEG-Local) que incluyó médicos especialistas y metodólogos. El GEG-Local formuló siete preguntas clínicas que ser respondidas en la presente GPC. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, estudios primarios en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La calidad de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG-Local usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y tratamiento. Finalmente, la GPC fue aprobada con Resolución N.° 47 ­ IETSI ­ ESSALUD ­ 2018. Resultados: La presente GPC abordó siete preguntas clínicas, respecto a dos temas: la evaluación inicial y el tratamiento de la estenosis aórtica severa. Con base en dichas preguntas se formularon nueve recomendaciones (una recomendación fuerte y ocho recomendaciones débiles), 16 puntos de buena práctica clínica y un flujograma. Conclusión: El presente artículo resume la metodología y las conclusiones de la GPC para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud.

Guía de práctica clínica para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el Seguro Social del Perú / Clinical practice guideline for the evaluation and management of patients with severe aortic stenosis for the Peruvian Social Security

Resumen Introducción: El presente artículo resume la guía de práctica clínica (GPC) para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud basadas en evidencia científica. Métodos: Se conformó un grupo elaborador local (GEG-Local) que incluyó médicos especialistas y metodólogos. El GEG-Local formuló siete preguntas clínicas que ser respondidas en la presente GPC. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, estudios primarios en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La calidad de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG-Local usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y tratamiento. Finalmente, la GPC fue aprobada con Resolución N.° 47 — IETSI — ESSALUD — 2018. Resultados: La presente GPC abordó siete preguntas clínicas, respecto a dos temas: la evaluación inicial y el tratamiento de la estenosis aórtica severa. Con base en dichas preguntas se formularon nueve recomendaciones (una recomendación fuerte y ocho recomendaciones débiles), 16 puntos de buena práctica clínica y un flujograma. Conclusión: El presente artículo resume la metodología y las conclusiones de la GPC para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud.

Abstract Introduction: This article summarizes the clinical practice guide (CPG) for the evaluation and management of patients with severe aortic stenosis in the Social Security of Peru (EsSalud). Objective: To provide clinical evidence-based recommendations for the evaluation and management of patients with severe aortic stenosis in the EsSalud. Methods: A local guideline development group (local GDG) was established, including medical specialists and methodologists. The local GDG formulated 7 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and, when it was considered pertinent, primary studies, were conducted in PubMed during 2018. The evidence to answer each of the posed clinical questions was selected. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice, and the flowchart of evaluation and management. Finally, the CPG was approved with Resolution N.° 47 — IETSI — ESSALUD — 2018. Results: This CPG addressed 7 clinical questions regarding two issues: the initial evaluation and the management of severe aortic stenosis. Based on these questions, 9 recommendations (1 strong recommendation and 8 weak recommendations), 16 points of good clinical practice, and 1 flowchart were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions from the CPG for the evaluation and management of patients with severe aortic stenosis in the EsSalud.

Assessment of Subclinical Left Ventricular Dysfunction in Aortic Stenosis.

Left ventricular (LV) systolic dysfunction is an adverse consequence of the pressure overload of severe aortic stenosis (AS). The enlargement of the interstitial space with reactive fibrosis and subsequently with replacement fibrosis and cell death has been suggested to be the main driver of the transition to symptoms, heart failure, and adverse cardiovascular events even after aortic valve replacement (AVR). Early and accurate recognition of myocardial dysfunction offers the potential to optimize the timing of intervention in severe AS. In the asymptomatic patient, an LV ejection fraction (EF) cutpoint of <50% has been used for this purpose. However, in most asymptomatic patients, an LVEF <50% is uncommon, and patients with an LVEF of 50% to 59% fare almost as badly. Moreover, the presence of a small LV cavity, the reliability and automation of the global longitudinal strain (GLS) signal, and the independent prognostic role of GLS are reasons why GLS could be expected to be a better marker of subclinical LV dysfunction in these patients. This review seeks to define whether the existing EF cutoff in AS should be modified or whether GLS should replace it as the marker of subclinical LV dysfunction.

Take home messages with cases from focused update on echocardiographic assessment of aortic stenosis.

Echocardiography plays an important role in the assessment of valvular aortic stenosis. Updated recommendations focusing on a stepwise approach to evaluating aortic stenosis have recently been published by the European Association of Cardiovascular Imaging and the American Society of Echocardiography. This review uses illustrative cases to demonstrate technical aspects of aortic stenosis assessment and use of the new proposed classification scheme for aortic stenosis. Key points from the updated recommendations reviewed in this paper are: (1) technical considerations and sources of error in measurement of peak velocity, mean aortic valve gradient and aortic valve area by continuity equation. (2) Application of flow status using indexed left ventricular stroke volume to distinguish patients with low gradients and a low calculated aortic valve area. (3) Use of low-dose dobutamine stress echocardiography in patients with low ejection fraction. (4) Application of the new classification scheme and review of algorithm use for echocardiographic evaluation of severe aortic stenosis. Improved understanding of how to handle unmatched variables and adopting an integrated approach to determine severity is central to guiding the clinician's management of aortic stenosis.

Systematic review of model-based economic evaluations of heart valve implantations.

OBJECTIVE: To review the evidence on the cost-effectiveness of heart valve implantations generated by decision analytic models and to assess their methodological quality. METHODS: A systematic review was performed including model-based cost-effectiveness analyses of heart valve implantations. Study and model characteristics and cost-effectiveness results were extracted and the methodological quality was assessed using the Philips checklist. RESULTS: Fourteen decision-analytic models regarding the cost-effectiveness of heart valve implantations were identified. In most studies transcatheter aortic valve implantation (TAVI) was cost-effective compared to standard treatment (ST) in inoperable or high-risk operable patients (ICER range 18,421-120,779 €) and in all studies surgical aortic valve replacement (SAVR) was cost-effective compared to ST in operable patients (ICER range 14,108-40,944 €), but the results were not consistent on the cost-effectiveness of TAVI versus SAVR in high-risk operable patients (ICER range: dominant to dominated by SAVR). Mechanical mitral valve replacement (MVR) had the lowest costs per success compared to mitral valve repair and biological MVR. The methodological quality of the studies was moderate to good. CONCLUSION: This review showed that improvements can be made in the description and justification of methods and data sources, sensitivity analysis on extrapolation of results, subgroup analyses, consideration of methodological and structural uncertainty, and consistency (i.e. validity) of the models. There are several opportunities for future decision-analytic models of the cost-effectiveness of heart valve implantations: considering heart valve implantations in other valve positions besides the aortic valve, using a societal perspective, and developing patient-simulation models to investigate the impact of patient characteristics on outcomes.

The impact of waiting for intervention on costs and effectiveness: the case of transcatheter aortic valve replacement.

OBJECTIVES: The economic crisis in Europe might have limited access to some innovative technologies implying an increase of waiting time. The purpose of the study is to evaluate the impact of waiting time on the costs and benefits of transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis. METHODS: This is a cost-utility analysis from the perspective of the Spanish National Health Service. Results of two prospective hospital registries (158 and 273 consecutive patients) were incorporated into a probabilistic Markov model to compare quality adjusted life years (QALYs) and costs for TAVR after waiting for 3-12 months, relative to immediate TAVR. We simulated a cohort of 1000 patients, male, and 80 years old; other patient profiles were assessed in sensitivity analyses. RESULTS: As waiting time increased, costs decreased at the expense of lower survival and loss of QALYs, leading to incremental cost-effectiveness ratios for eliminating waiting lists of about 12,500 € per QALY. In subgroup analyses prioritization of patients for whom higher benefit was expected led to a smaller loss of QALYs. Concerning budget impact, long waiting lists reduced spending considerably and permanently. CONCLUSIONS: A shorter waiting time is likely to be cost-effective (considering commonly accepted willingness-to-pay thresholds in Europe) relative to 3 months or longer waiting periods. If waiting lists are nevertheless seen as unavoidable due to severe but temporary budgetary restrictions, prioritizing patients for whom higher benefit is expected appears to be a way of postponing spending without utterly sacrificing patients' survival and quality of life.

Gender-related differences on short- and long-term outcomes of patients undergoing transcatheter aortic valve implantation.

OBJECTIVES: This study aimed to compare gender-related differences in outcomes of patients undergoing TAVI over a long-term follow-up period. BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been considered the standard therapy for patients with inoperable or high-risk symptomatic aortic stenosis. The influence of gender-related differences in outcomes of patients undergoing TAVI is currently on debate. METHODS: From January 2008 to January 2015, 819 patients (49% men) underwent TAVI and were included in a multicenter Brazilian registry. Patients were followed-up and clinical outcomes were evaluated according to the updated Valve Academic Research Consortium-2 criteria. RESULTS: Mean follow-up was 497 ± 478 days. Compared with women, men had a lower rate of major or life-threatening bleeding (12.0% vs. 20.6%; HR = 0.57 [95CI% 0.40-0.81]; P = 0.001), and major vascular complications (6% vs. 11.7%; HR = 0.50 [95CI% 0.31-0.82]; P = 0.004). At 30 days, all-cause mortality was lower in men than in women (6.5% vs. 11.5%; P = 0.013), however, cumulative all-cause mortality was similar between groups (25.9% vs. 29.7%, men and women, respectively, HR = 0.92 [95CI% 0.71-1.19]; P = 0.52) over the entire follow-up period. By adjusted Cox regression model, renal function, diabetes, peripheral artery disease, and chronic obstructive pulmonary disease (COPD) remained independently predictors of all-cause mortality. CONCLUSIONS: In this large-scale study evaluating patients undergoing TAVI, 30-day mortality was higher among women than men driven by significant higher rates of major or life-threatening bleeding and major vascular complications. However, all-cause mortality on long-term follow-up was similar between groups. © 2016 Wiley Periodicals, Inc.