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Introducción: El incremento exponencial de la incidencia de la estenosis aórtica en relación con la edad, al igual que la presencia de factores de riesgo como el síndrome metabólico, predisponen a la calcificación aórtica como una manifestación de enfermedad cardiovascular generalizada. Objetivo: Identificar las incongruencias existentes entre las manifestaciones clínicas y el estudio ecocardiográfico en pacientes con estenosis valvular aórtica severa. Materiales y métodos: Se realizó un estudio descriptivo-analítico en una muestra conformada por 50 pacientes diagnosticados, clínica y ecográficamente, de estenosis aórtica severa. Resultados: Se halló predomino de féminas blancas de la tercera edad con historia de dolor anginoso y disnea, acompañados de soplo mesosistólico intenso en foco aórtico, y un segundo ruido débil, y cifras tensionales bajas con pocos criterios ultrasonográficos de hipertrofia del ventrículo izquierdo y velocidad pico, unido al gradiente y el área aórtica, sugestivos de estenosis severa en un elevado por ciento, con calcificación de válvulas y una fracción de eyección del ventrículo izquierdo elevada, junto a la presencia de otras valvulopatías. Conclusiones: El estudio demostró pobre correlación entre las manifestaciones clínicas y las ecocardiográficas.

Introduction: The exponential increase of aortic stenosis incidence in relation to age, as well as the presence of risk factors such as metabolic syndrome, predispose to aortic calcification as a manifestation of a generalized cardiovascular disease. Objective: To identify the incongruences existing between clinical manifestations and the echocardiographic study in patients with severe aortic valvular stenosis. Materials and methods: An analytical-descriptive study was carried out in a sample of 50 patients clinically and echo-graphically diagnosed of severe aortic stenosis. Results: A predominance of elder white women with a history of anginous pain and dyspnea was found, accompanied of intense meso-systolic murmur in aortic focus, and a second weak sound, and low blood tension figures with few ultrasonographic criteria of left ventricular hypertrophy and peak velocity, together with gradient and aortic area, which suggest a high-percent of severe stenosis, with valvular calcification and an elevated left ventricular elevation fraction, plus the presence of other valvular diseases. Conclusions: The study showed poor relationship between clinical and echocardiography manifestations.

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As the population continues to grow, and life expectancy has increased, aortic stenosis (AS) has become the most common valvular disease requiring surgical treatment. The evolution of valve replacement therapies has progressed significantly since 1960. In the last 20 years, transcatheter aortic valve implantation (TAVI) has been a game changer, and has potential to become the standard of care. Despite uncertain prognosis benefits, balloon aortic valvuloplasty (BAV) can be useful in a broad range of patients with AS, as well as being a bridging therapy to valve replacement, or as a destination therapy, besides its role in TAVI procedures. This review describes the contemporary role of BAV in AS treatment, and focuses on technical improvements that reframe BAV as an effective tool in a variety of clinical scenarios. One of these improvements is transradial BAV, either with the conventional approach of BAV or applying the bilateral technique with two balloons.

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BACKGROUND: The comparative mid and long-term durability, including the rates of bioprosthetic valve failure (BVF) of the Sapien XT® and Sapien 3® transcatheter heart valve (THV) in patients with intermediate surgical risk has not been reported. METHODS: Consecutive intermediate-risk patients with severe aortic stenosis from the Mexican registry of transcatheter aortic valve replacement (TAVR) with Sapien® THVs were included. The primary endpoint was to compare the BVF rate between THVs at 2 years of follow-up. Secondary endpoints were comparisons of the composite of global mortality, cardiovascular mortality, and neurological events at 30 d and 24 months of follow-up. RESULTS: During 2014-2019, 115 (60 Sapien XT® and 55 Sapien 3®) patients met the inclusion criteria in five medical centres. The mean age was 77.3 ± 8.4 years. The average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) was 5.6 ± 2.9. There was no statistically significant difference between the groups in BVF rate. At 30 d, overall, cardiovascular and non-cardiovascular mortality was 4.3%, 2.6%, and 1.7%, respectively. Neurological events rate was 1.73%. The mean long-term follow-up was 25.3 ± 14.2 months with an overall mortality of 9.56% but lower for the Sapien 3® group (15% vs. 3.6%, p=.037). The only independent predictor of composite mortality and neurological events that occurred in the long term was using a Sapien XT® [OR 1.6, CI 95%, 1.0-24.9; p=.049]. CONCLUSIONS: The BVF rate at 25 months of follow-up was similar with the XT and S3 systems. During this follow-up period, the major composite events of death from any cause and neurological events were significantly lower with the S3 system.

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OBJECTIVE: Although current guidelines generally recommend watchful waiting strategy for patients with asymptomatic severe aortic stenosis until symptoms develop, early surgery for asymptomatic aortic stenosis remains controversial. This study aimed to compare the outcomes of early surgery versus conservative strategy for patients with asymptomatic severe aortic stenosis. METHODS: MEDLINE and EMBASE were searched through February 2020 to identify clinical trials that investigated early surgery and conservative strategy for patients with asymptomatic severe aortic stenosis. From each study, we extracted the hazard ratio of all-cause mortality and cardiovascular mortality. Subgroup analyses were conducted by dividing into severe aortic stenosis (peak aortic jet velocity ≥4.0 m/s, mean aortic pressure gradient ≥40 mm Hg, or aortic valve area ≤1.0 cm2) and very severe aortic stenosis (peak aortic jet velocity ≥4.5 m/s, mean pressure gradient ≥50 mm Hg, or aortic valve area ≤0.75 cm2) groups. RESULTS: One randomized controlled trial and 7 observational studies were identified. Pooled analyses demonstrated that all-cause mortality and cardiovascular mortality for early surgery were significantly lower compared with conservative strategy (hazard ratio, 0.49; 95% confidence interval, 0.36-0.68; P < .0001, hazard ratio, 0.42; 95% confidence interval, 0.22-0.82; P = .01, respectively). Subgroup analyses showed significant reduction for early surgery in all-cause mortality (severe aortic stenosis: hazard ratio, 0.52; 95% confidence interval, 0.35-0.78; P = .001, very severe aortic stenosis: hazard ratio, 0.38; 95% confidence interval, 0.17-0.85; P = .02). CONCLUSIONS: We demonstrated that early surgery was associated with significant reduction in all-cause and cardiovascular mortality in patients with severe aortic stenosis. Further randomized trials are warranted to confirm our findings.

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BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disease, caused by mutations in the gene encoding the enzyme α-galactosidase A (α-Gal A). Cardiac involvement is one of the main causes of death and it is characterized by progressive concentric left ventricular hypertrophy (LVH), which in most cases is symmetric. Mild thickening of the left-sided valves is seen in as many as a quarter of patients. Severe aortic stenosis is an extremely rare disorder in FD. CASE SUMMARY: In this report, we describe the case of a 57-year-old male, who was diagnosed with a cardiac variant of FD 10 years ago. Since the patient had severe LVH, he was started on enzyme replacement therapy when he was 47 years old with an intravenous infusion of 0.2 mg/kg of agalsidase alpha every 14 days. The patient remained stable and asymptomatic for 9 years, until he presented with dyspnoea in New York Heart Association functional class II-III and severe aortic stenosis (aortic valve area: 0.97 cm2) together with severe systolic dysfunction [ejection fraction (EF): 29%]. Because of the patient's comorbidities and high surgical risk, he underwent successful transfemoral transcatheter aortic valve implantation (TAVI). At 2 months following TAVI, the patient was asymptomatic and, in spite of his Fabry cardiomyopathy, the EF had increased to 45%. DISCUSSION: To our knowledge, this is the first case in the literature to demonstrate a rapid progression of aortic stenosis with severe impairment of left ventricular function and worsening in functional class in a patient with FD, who following TAVI improved his EF, with disappearance of symptoms and ventricular arrhythmias.

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O desenvolvimento de novas técnicas para o tratamento eficaz da estenose valvar aórtica grave (EAo) é necessário para reduzir a morbimortalidade do procedimento cirúrgico. O implante transcateter de válvula aórtica (TAVI) surgiu com essa finalidade. As avaliações econômicas (AE) podem fornecer informações sobre qual tecnologia é custo-efetiva para a saúde, de acordo com a quantidade de recursos usados. As revisões sistemáticas (RS) dos estudos de EA são ferramentas relevantes para avaliar os métodos usados nesses estudos. Objetivo: Foi realizada uma RS de EA completa que avaliou o TAVI no tratamento de EAo grave em pacientes com risco cirúrgico alto e intermediário. Metodologia: Foi realizada pesquisa nas seguintes bases de dados: Medline, EMBASE, CRD NHS EED e The Cochrane Library, de janeiro a julho de 2019, sobre a utilização do TAVI no tratamento da estenose aórtica grave. Resultados: Foram incluídos 16 estudos completos de EA. Cinco usaram modelagem de Markov, um Markov e Monte Carlo e árvore de decisão. Quinze estudos usaram horizontes de tempo entre 1 e 15 anos e um para toda a vida. Cinco usaram taxa de desconto que variou de 1,5 a 5%. As fontes de dados de eficácia foram obtidas principalmente de dados secundários, principalmente do estudo pioneiro PARTNER. Normalmente, os benefícios e custos eram maiores para TAVI em comparação com SAVR. O TAVI foi dominante em cinco cenários, em dois foi dominado e nos demais a maioria apresentou evidências de custo-efetividade. A qualidade dos estudos demonstrou pontos frágeis, minimizando a transparência do relato dos itens. Conclusão: Os estudos analisados não apresentam dados de forma padronizada, impedindo comparações precisas entre as metodologias e os resultados obtidos. Houve uma limitação para avaliar o desfecho do TAVI por considerar o TAVI uma tecnologia para tratar uma doença crônica, e por apresentar ausência de Markov e fragilidade no item horizonte de tempo, por não ter utilizado igual à expectativa de vida dos indivíduos, como recomendado para doenças crônicas. Comumente, as análises que apresentaram maior qualidade e utilizaram um modelo analítico mostraram que o TAVI é uma opção custo-efetiva em pacientes com EAo grave com risco cirúrgico intermediário ou alto

The development of new techniques for the effective treatment of severe aortic valve stenosis (AS) is necessary to reduce the morbidity and mortality of the surgical procedure. The implant aortic valve transcatheter (TAVI) appeared with this finality. Economics assessments (EA) can provide information on which technology is cost-efetive for health by the amount of resources used. Systematic reviews (SR) of EA studies are relevant tools for evaluating the methods used in that studies. Objective: A SR of complete AE that assessed TAVI in the treatment of severe AoS in patients with high and intermediate surgical risk was performed. Methodology: Research was carried out on the following databases: Medline, EMBASE, CRD NHS EED and The Cochrane Library, from January to July 2019, on the use of TAVI in the treatment of the stenosis aortic severe. Results: It 16 complete EA studies were included. Five used Markov modeling, one Markov and Monte Carlo and decision tree. Fifteen studies used time horizons between 1 and 15 years and one to for whole life. Five used discount rate that varied from 1.5 to 5%. The sources of effectiveness data were mostly obtained from secondary data, mainly from the pioneer PARTNER study. Usually, the benefits and costs were bigger for TAVI compared to SAVR. TAVI was dominant in five scenarios, in two it was dominated and in the others, most presented evidence cost-effectiveness. The quality of the studies demonstrated fragile points, minimizing the transparency of the reporting of the items. Conclusion: The analyzed studies do not present data in a standardized manner, preventing accurate comparisons between the methodologies and results obtained. There was a limitation to assess TAVI upshot considering TAVI a technology to treat a chronic disease, and for presenting absence of Markov and fragility in the time horizon item, for not having used equal to the life expectancy of individuals, as recommended for chronic diseases. Commonly, the analysis that presented higher quality and used an analytical model have shown that TAVI is a cost-effective option in patients with severe AS with intermediate or high surgical risk.

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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.

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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.

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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.

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Resumen La estenosis aórtica severa de flujo bajo, gradiente bajo y la fracción de eyección del ventrículo izquierdo conservada es una entidad frecuente en la práctica clínica. Probablemente, represente una fase más avanzada de la enfermedad con una mayor carga soportada o de más larga data y con una fisiopatología restrictiva. Existen características clínicas, hemodinámicas y ecocardiográficas típicas. Se trata de una entidad infradiagnosticada y como consecuencia infratratada con un claro peor pronóstico con tratamiento conservador. Se necesita en muchos casos el apoyo de la «multiimagen¼ para un adecuado diagnóstico y elección del momento terapéutico. La sustitución valvular en los pacientes con estenosis aórtica severa y flujo bajo paradójico, parecen tener una mayor mortalidad a corto y largo plazo al compararla en los pacientes con flujo normal y similar si lo hacemos frente a la estenosis aórtica de bajo flujo y fracción de eyección del ventrículo izquierdo deprimida. Existe una menor mortalidad con la implantación transcatéter de válvula aórtica comparándolo frente al tratamiento médico en pacientes con estenosis aórtica severa sintomática con flujo bajo, tanto la fracción de eyección baja como el flujo bajo paradójico, considerados inoperables. No parecen existir evidencias actuales para recomendar el abordaje percutáneo frente al recambio valvular aórtico quirúrgico en los pacientes de alto riesgo quirúrgico con estenosis aórtica con flujo bajo paradójico.

Abstract Low-flow, low-gradient severe aortic stenosis with preserved ejection fraction of the left ventricle is a frequent entity of clinical practice. It can probably represent a more advance phase of the illness with a heavier load or time frame and a restrictive pathophysiology. There are typical clinical, hemodynamic and echocardiographic characteristics. It is an underdiagnosed condition, and as such it is undertreated, with a clearly worse prognosis with conservative treatment. In many cases, the help of «multiimaging¼ is required for an appropriate diagnosis and choosing the therapeutic moment. Valve replacement in patients with paradoxical low-flow, low-gradient severe aortic stenosis seem to show higher mortality in the short and long term when compared to patients with normal flow, and similar mortality if compared to low-flow aortic stenosis with depressed ejection fraction of the left ventricle. There is a lower mortality with the transcatheter aortic valve implantation in comparison with treatment of patients with symptomatic low-flow severe aortic stenosis, both for a low ejection fraction and for the paradoxical low flow, considered inoperable. No current evidence seems to exist to recommend percutaneous approach versus aortic valve replacement in high surgical risk patients with aortic stenosis with paradoxical low flow severe aortic stenosis.

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INTRODUCTION: There is scarce information about right ventricle (RV) function in patients with secondary pulmonary hypertension (PH) undergoing transcatheter aortic valve implantation (TAVI). We aim to identify possible RV abnormalities in patients referred for TAVI with severe aortic stenosis (sAS) and secondary PH. METHODS: Objective measures of RV function, as well as noninvasive estimates of pulmonary artery systolic pressures (PASP) were obtained from 30 sAS patients undergoing percutaneous valve intervention. RESULTS: Sixteen (53%) evaluated patients had some degree of PH. As expected, left ventricular mass index (281 ± 75 g/m2) and left atrial volume index (89 ± 23 mL/m2) values were significantly elevated. Even though RV end-systolic (8 ± 4 cm2) and end-diastolic (17 ± 4 cm2) areas were normal as well as RV fractional area change values (57 ± 16%); both longitudinal measures of RV systolic function such as tricuspid annular plane systolic excursion (1.9 ± 0.5 cm) and systolic velocity (10 ± 2 cm/s) were clearly reduced with just mild elevations in PASP (54 ± 7 mmHg). CONCLUSIONS: Subclinical RV dysfunction is present in patients with sAS and secondary PH undergoing TAVI. Whether longitudinal measures of RV systolic function could predict clinical outcomes in these patients needs to be further explored.

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BACKGROUND: Patients with severe aortic stenosis have increased levels of prothrombotic and proinflammatory microparticles (MP), and MPs actively regulate pathological processes that lead to atherothrombotic cardiovascular events. Shear stress is a validated stimulus of MP production, and abnormal shear stress in aortic stenosis increases MP release in ex-vivo studies. We hypothesized that in patients with severe aortic stenosis, percutaneous replacement of the aortic valve (TAVR) would reduce abnormal shear stress and would decrease levels of circulating MPs. FINDINGS: The experimental protocol utilized flow cytometry (FC) and nanoparticle tracking analysis (NTA) to quantify circulating plasma MP levels in aortic stenosis patients at baseline and 5 days after TAVR. The baseline and 5 day MP counts measured by FC were 6.10⋅10(5) ± 1.21⋅10(5) MP/µL and 5.74⋅10(5) ± 9.54⋅10(4) MP/µL, respectively (p = 0.91). The baseline and 5 day MP counts measured by NTA were 9.29⋅10(13) ± 1.66⋅10(13) MP/µL and 3.95⋅10(14) ± 3.11⋅10(14) MP/µL, respectively (p = 0.91). When MPs were stratified by cell source, there was no difference in pre/post TAVR endothelial, platelet, or leukocyte MP levels. CONCLUSION: Levels of circulating MPs do not change acutely following TAVR therapy for aortic stenosis. Trial registered at clinicaltrials.gov NCT02193035 on July 11, 2014.

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BACKGROUND: Severe aortic stenosis (AS), leads to pathological left ventricular remodeling that may worsen with concomitant overweight and obesity (OW/O). METHODS: We aimed to prospectively analyze the impact of OW/O on ventricular remodeling in severe AS, by evaluating the percentage of intraendomyocardial fibrosis (PIEF) and the percentage of infiltrating intraendocardial lipid vacuoles (PIELV) and its relationship to global longitudinal strain (GLS) in patients with OW/O. RESULTS: 44 patients with severe AS were included, 13 non-obese (29%) and 31 OW/O (71%), all of them with left ventricular ejection fraction ≥ 55%. GLS was evaluated with 2D speckle tracking. During valve replacement, an endocardial biopsy was obtained, where PIEF and PIELV were analyzed. Patients with higher PIEF and PIELV had greater body mass index (p < 0.0001) and worse GLS (p < 0.0053). A GLS cut-off point < -14% had a sensitivity of 75%, and a specificity of 92.8% to detect important PIEF (AUC: 0.928, 95% confidence interval: 0.798-1.00). On multivariate analysis, OW/O and PIELV were independently associated to the PIEF, and OW/O and PIEF were independently associated to GLS. A high correlation between the amount of PIELV and PIEF were found. CONCLUSION: Patients with severe AS and OW/O have greater PIEF and PIELV, suggesting more pathological remodeling. GLS is useful to detect subclinical myocardial injury and is potentially useful for endomyocardial fibrosis detection. The presence of higher PIELF may be a trigger factor for the development of intraendomyocardial fibrosis.

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Introducción: En la estenosis aórtica sintomática grave (EASG), la alteración del strain global longitudinal sistólico (SGLS) tendría correlación con las modificaciones de la histoarquitectura y podría identificar compromiso contráctil temprano en pacientes con fracción de eyección conservada (FEyC). Objetivo: Analizar el SGLS, el volumen de colágeno (VC), el área miocitaria (ArMi) y el compromiso contráctil en pacientes con EASG y FEyC. Material y métodos: Se incorporaron 26 pacientes con EASG y FEyC (edad 67 ± 11 años, 53% hombres). Se realizaron un estudio hemodinámico preoperatorio y una biopsia endomiocárdica intraoperatoria para determinar el VC y el ArMi. Se identificaron tres grupos de pacientes: G1, hipertrofia ventricular izquierda (HVI) compensada sin enfermedad coronaria (n = 8); G2, HVI descompensada sin enfermedad coronaria (n = 7) y G3, HVI descompensada con enfermedad coronaria (n = 11). El SGLS se normalizó por volumen sistólico, estrés meridional de fin de sístole (δ) y diámetro de fin de diástole (DFD). Resultados: G1, G2 y G3, sin diferencias en volumen sistólico, δ y DFD y con diferencias en VC (%) (G1: 4,7 ± 1,2; G2: 8,4 ± 1,2; G3: 11,0 ± 3,0; p < 0,01), ArMi (mm²) (G1: 328,7 ± 66,2; G2: 376,7 ± 21,9; G3: 385,0 ± 13,0; p = 0,01), PFDVI (mm Hg) (G1: 13,1 ± 1,5; G2: 19,0 ± 3,8; G3: 23,6 ± 5,8; p < 0,01), +dP/dt máx (mm Hg/seg / PFDVI, mm Hg) (G1: 176,4 ± 45,5; G2: 89,6 ± 20,1; G3: 113,1 ± 43,7; p < 0,01), SGLS (%) (G1: -17,9 ± 4,2; G2: -13,5 ± 2,5; G3: -13,6 ± 3; p = 0,021). El SGLS se correlacionó con VC y PFDVI y hubo tendencia con un índice de contractilidad (+dP/dt máx mm Hg/seg / PFDVI, mm Hg). Conclusiones: Las alteraciones del SGLS en pacientes con EASG y FEyC son expresión de alteraciones estructurales del miocardio relacionadas con incremento del VC, asociado con un aumento de la PFDVI y con probable falla miocárdica contráctil.(AU)

Background: In severe symptomatic aortic stenosis (SSAS) altered global longitudinal systolic strain (GLSS) would correlate with changes in myocardial histological architecture and could identify early contractile involvement in patients with preserved ejection fraction (PEF). Objective: The aim of this study was to analyze GLSS, collagen volume (CV), myocyte area (MyAr) and contractile involvement in patients with SSAS and PEF. Methods: Twenty six patients with SSAS and PEF (67±11 years old, 53% male) were included in the study. A preoperative hemodynamic study and an intraoperative endomyocardial biopsy were performed to determine CV and MyAr. Three groups of patients were identified: G1: compensated left ventricular hypertrophy (LVH) without coronary disease (n=8); G2: decompensated LVH without coronary disease (n=7) and G3: decompensated LVH with coronary disease (n=11). GLSS was normalized by stroke volume, meridional end-systolic wall stress (δ) and end-diastolic diameter (EDD). Results: No significant differences in stroke volume, δ and EDD were observed between groups G1, G2 and G3. Differences between groups were observed in: CV (%) (G1: 4.7 ± 1.2, G2: 8.4 ± 1.2, G3: 11.0 ± 3.0; p < 0.01), MyAr (mm²) (G1: 328.7 ± 66.2, G2: 376.7 ± 21.9, G3: 385.0 ± 13.0; p = 0.01), LVEDP (mm Hg) (G1: 13.1 ± 1.5, G2: 19.0 ± 3.8, G3: 23.6 ± 5.8; p < 0.01), +dP/dt max (mm Hg/sec / LVEDP, mm Hg) (G1: 176.4 ± 45.5, G2: 89.6 ± 20.1, G3: 113.1 ± 43.7; p < 0.01), and GLSS (%) (G1: -17.9 ± 4.2, G2: -13.5 ± 2.5, G3: -13.6 ± 3; p = 0.021). GLSS correlated with CV and LVEDP and it evidenced a trend to correlate with a contractility index (+dP/dt max mm Hg/s / LVEDP, mm Hg). Conclusions: Altered GLSS in patients with SSAS and PEF expresses myocardial structural changes related to increase in C V, which is associated with enhanced LVEDP and probable myocardial contractile failure.(AU)

RESUMEN

Introducción: En la estenosis aórtica sintomática grave (EASG), la alteración del strain global longitudinal sistólico (SGLS) tendría correlación con las modificaciones de la histoarquitectura y podría identificar compromiso contráctil temprano en pacientes con fracción de eyección conservada (FEyC). Objetivo: Analizar el SGLS, el volumen de colágeno (VC), el área miocitaria (ArMi) y el compromiso contráctil en pacientes con EASG y FEyC. Material y métodos: Se incorporaron 26 pacientes con EASG y FEyC (edad 67 ± 11 años, 53% hombres). Se realizaron un estudio hemodinámico preoperatorio y una biopsia endomiocárdica intraoperatoria para determinar el VC y el ArMi. Se identificaron tres grupos de pacientes: G1, hipertrofia ventricular izquierda (HVI) compensada sin enfermedad coronaria (n = 8); G2, HVI descompensada sin enfermedad coronaria (n = 7) y G3, HVI descompensada con enfermedad coronaria (n = 11). El SGLS se normalizó por volumen sistólico, estrés meridional de fin de sístole (δ) y diámetro de fin de diástole (DFD). Resultados: G1, G2 y G3, sin diferencias en volumen sistólico, δ y DFD y con diferencias en VC (%) (G1: 4,7 ± 1,2; G2: 8,4 ± 1,2; G3: 11,0 ± 3,0; p < 0,01), ArMi (mm²) (G1: 328,7 ± 66,2; G2: 376,7 ± 21,9; G3: 385,0 ± 13,0; p = 0,01), PFDVI (mm Hg) (G1: 13,1 ± 1,5; G2: 19,0 ± 3,8; G3: 23,6 ± 5,8; p < 0,01), +dP/dt máx (mm Hg/seg / PFDVI, mm Hg) (G1: 176,4 ± 45,5; G2: 89,6 ± 20,1; G3: 113,1 ± 43,7; p < 0,01), SGLS (%) (G1: -17,9 ± 4,2; G2: -13,5 ± 2,5; G3: -13,6 ± 3; p = 0,021). El SGLS se correlacionó con VC y PFDVI y hubo tendencia con un índice de contractilidad (+dP/dt máx mm Hg/seg / PFDVI, mm Hg). Conclusiones: Las alteraciones del SGLS en pacientes con EASG y FEyC son expresión de alteraciones estructurales del miocardio relacionadas con incremento del VC, asociado con un aumento de la PFDVI y con probable falla miocárdica contráctil.

Background: In severe symptomatic aortic stenosis (SSAS) altered global longitudinal systolic strain (GLSS) would correlate with changes in myocardial histological architecture and could identify early contractile involvement in patients with preserved ejection fraction (PEF). Objective: The aim of this study was to analyze GLSS, collagen volume (CV), myocyte area (MyAr) and contractile involvement in patients with SSAS and PEF. Methods: Twenty six patients with SSAS and PEF (67±11 years old, 53% male) were included in the study. A preoperative hemodynamic study and an intraoperative endomyocardial biopsy were performed to determine CV and MyAr. Three groups of patients were identified: G1: compensated left ventricular hypertrophy (LVH) without coronary disease (n=8); G2: decompensated LVH without coronary disease (n=7) and G3: decompensated LVH with coronary disease (n=11). GLSS was normalized by stroke volume, meridional end-systolic wall stress (δ) and end-diastolic diameter (EDD). Results: No significant differences in stroke volume, δ and EDD were observed between groups G1, G2 and G3. Differences between groups were observed in: CV (%) (G1: 4.7 ± 1.2, G2: 8.4 ± 1.2, G3: 11.0 ± 3.0; p < 0.01), MyAr (mm²) (G1: 328.7 ± 66.2, G2: 376.7 ± 21.9, G3: 385.0 ± 13.0; p = 0.01), LVEDP (mm Hg) (G1: 13.1 ± 1.5, G2: 19.0 ± 3.8, G3: 23.6 ± 5.8; p < 0.01), +dP/dt max (mm Hg/sec / LVEDP, mm Hg) (G1: 176.4 ± 45.5, G2: 89.6 ± 20.1, G3: 113.1 ± 43.7; p < 0.01), and GLSS (%) (G1: -17.9 ± 4.2, G2: -13.5 ± 2.5, G3: -13.6 ± 3; p = 0.021). GLSS correlated with CV and LVEDP and it evidenced a trend to correlate with a contractility index (+dP/dt max mm Hg/s / LVEDP, mm Hg). Conclusions: Altered GLSS in patients with SSAS and PEF expresses myocardial structural changes related to increase in C V, which is associated with enhanced LVEDP and probable myocardial contractile failure.

RESUMEN

Introducción: La estenosis aórtica severa impacta la morbilidad y mortalidad de los pacientes. Ésta se define como un área valvular menor a 1 cm² o menor a 0,6 cm²/m² de superficie corporal, gradientes transvalvulares mayores a 40 mm Hg y velocidades pico mayores a 4 m/s. Cuando los pacientes tienen estenosis aórtica severa y fracción de expulsión del ventrículo izquierdo conservada, se espera que estos valores sean elevados, pero se ha encontrado un subgrupo donde estos valores son menores, hecho que ha llevado a revaluar los puntos de corte para definir dicha enfermedad. Objetivo: Evaluar la prevalencia de estenosis aórtica severa con fracción de expulsión preservada de bajo flujo paradójico y determinar las características hemodinámicas e impacto clínico en los pacientes. Métodos: Estudio retrospectivo llevado a cabo durante 1999-2010, en un servicio de ecocardiografía, en el que se evaluaron 839 pacientes con diagnóstico de estenosis aórtica severa y fracción de eyección del ventrículo izquierdo conservada. La muestra fue subdividida en dos grupos: flujo normal definido como un volumen latido indexado (VLI) > 35 mL/m² y grupo bajo flujo paradójico con un VLI ≤ 35 mL/m² y se evaluaron sus características hemodinámicas, valvulares y de geometría ventricular, además de la supervivencia. Resultados: El 49,1% se clasificó como bajo flujo paradójico y el 50,9% como flujo normal. La edad promedio de fue 66,4 años y el 56,1% eran mujeres. La presión arterial media promedio fue 92,5 mm Hg, el gradiente medio 41,2 mm Hg y la fracción de expulsión promedio de 60%. Al comparar ambos grupos se encontró que los pacientes con bajo flujo paradójico tenían mayor impedancia válvulo-arterial (6,2 versus 4,25 mm Hg/mL/m, p < 0,001), mayor diámetro diastólico (4,76 versus 4,62 cm, p < 0,001) y mayor resistencia vascular sistémica (2,18 versus 1,51 mm Hg*min/L, p < 0,001). No hubo diferencias en la supervivencia. Conclusión: La estenosis aórtica de bajo flujo paradójico y bajo gradiente, es una entidad frecuente que se asocia con mayor postcarga del ventrículo izquierdo. Para mejorar el tratamiento de estos pacientes se requiere revaluar los criterios diagnósticos y obtener una evaluación más profunda del funcionamiento miocárdico además de la fracción de expulsión del ventrículo izquierdo. Aunque no se hallaron diferencias en la supervivencia entre ambos grupos, los estudios previos alertan que estos pacientes requieren un seguimiento más estrecho y un mejor entendimiento de su fisiología.

Introduction: severe aortic stenosis impacts the morbidity and mortality of patients. It is defined as a valve area < 1 cm² or < than 0.6 cm²/m² of BSA, transvalvular gradients > 40 mm Hg and peak velocities > 4 m/s. When patients have severe aortic stenosis and preserved left ventricle ejection fraction, these values are expected to be high, but a subset of patients where these values are lower has been found and this fact has led to reassess the cutoff points to define the disease. Objective: To assess the prevalence of paradoxical low-flow/low-gradient severe aortic stenosis with preserved ejection fraction and determine the hemodynamic characteristics and clinical impact in patients. Methods: A retrospective study conducted during 1999-2010 in an echocardiography service, which evaluated 839 patients with severe aortic stenosis and preserved left ventricle ejection fraction. The sample was divided into two groups: normal flow group, defined as an indexed stroke volume > 35 mL /m² and paradoxical low-flow group, with indexed stroke volume ≤ 35 mL/m² and their hemodynamic characteristics, valvular and ventricular geometry as well as survival were evaluated. Results: 49.1% were classified as paradoxical low-flow and 50.9 % as normal flow. The average age was 66.4 years and 56.1% were women. The average mean arterial pressure was 92.5 mm Hg, mean gradient 41.2 mm Hg and mean ejection fraction 60%. When comparing the two groups, patients with paradoxical low flow had higher valvular-arterial impedance (6.2 versus 4.25 mm Hg/mL/m, p < 0.001), greater LV diastolic diameter (4.76 versus 4.62 cm, p < 0.001) and higher systemic vascular resistance (2.18 versus 1.51 mm Hg * min/L, p < 0.001). There was no differen ce in survival. Conclusion: Paradoxical low-flow/low-gradient aortic stenosis is a common entity that is associated with increased left ventricular afterload. To improve the treatment of these patients it is necessary to reassess the diagnostic criteria and obtain a more thorough evaluation of myocardial function in addition to the left ventricle ejection fraction. Although there was no difference in survival between the two groups, previous studies warn that these patients require closer monitoring and better understanding of their physiology.

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