Implante percutâneo de válvula aórtica (TAVI) para tratamento da estenose aórtica grave em pacientes inoperáveis / Percutaneous aortic valve implantation (TAVI) for treatment of severe aortic stenosis in patients inoperable

INTRODUÇÃO: A estenose aórtica é relacionada a fatores de risco para aterosclerose, principalmente ao envelhecimento. A prevalência na faixa etária entre 65 e 74 anos é de 1,3%, e acima de 75 anos, 2,8%. Pacientes com estenose aórtica têm risco aumentado de morte cardiovascular (HR 2,14; IC 95% 1,21-3,76). As manifestações clínicas são relacionadas à insuficiência cardíaca, podendo também estarem presentes dor no peito (angina) e síncope. O prognóstico, após início dos sintomas, é de 50% de mortalidade em dois anos, sendo recomendada a cirurgia de troca valvar aórtica, mas cerca de 30% dos idosos têm a cirurgia contraindicada pelo alto risco cirúrgico. O TAVI é uma opção de tratamento percutâneo (transapical ou transfemoral), com troca valvar sem necessidade de toracotomia e circulação extracorpórea. Apresenta benefícios em relação ao tratamento clínico tais como maior sobrevida e qualidade de vida, reduzindo sintomas relacionados à insuficiência cardíaca e o número de internações hospitalares, porém, associa-se com riscos imediatos como necessidade de implante de marcapasso, hemotransfusões, insuficiência renal, diálise, acidente vascular cerebral, lesões vasculares, tamponamento cardíaco e morte. Como os resultados de eficácia são distintos de acordo com a via de acesso à valva aórtica, este relatório contempla apenas TAVI por via transfemoral. TECNOLOGIA: Implante percutâneo transfemoral de válvula aórtica (TAVI). PERGUNTA DE PESQUISA: Em pacientes com estenose aórtica grave considerados inoperáveis, o TAVI, em comparação com o tratamento clínico, é seguro e custo-efetivo? EVIDÊNCIAS CLÍNICAS: Um ensaio randomizado (PARTNER B), além de registros e estudos observacionais, apresentaram ganhos em sobrevida e na qualidade de vida com o TAVI. Resultados de 5 anos do PARTNER B, com 179 pacientes em cada braço de intervenção, revelam menor mortalidade (71,8% versus 93,6%), HR 0,50 (IC95% 0,39-0,65), menor chance de hospitalização (47,6% versus 87,3%; p < 0,0001) e maior chance de estar em classe funcional NYHA I e II (New York Heart Association) (86% versus 60%) nos pacientes do grupo TAVI. Acidente vascular cerebral foi mais frequente até o seguimento de três anos do TAVI (14,4% TAVI versus 4,12% braço clínico; p = 0,0007). AVALIAÇÃO ECONÔMICA: Avaliação do tipo custo-utilidade em modelo de Markov, com ciclos mensais, horizonte temporal de 5 anos, perspectiva do SUS, revela razão de custo-utilidade incremental (RCUI) de R$189.920,69/QALY. Na análise de sensibilidade determinística, observou-se que o custo do TAVI é o parâmetro com maior impacto na RCUI. Considerando um limiar de 3 PIB per capita por ano de vida ajustado por qualidade (QALY) e analisando separadamente os componentes do custo TAVI como o custo do procedimento (considerado fixo e equivalente a R$ 28.244,41) e o custo da prótese (variável), estimou-se que, para o TAVI ser considerado custo-efetivo, o custo máximo do procedimento TAVI deve ser de R$ 57.292,1 e consequentemente, o custo máximo isolado da prótese equivalente a R$ 29.047,69. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário é proporcional à quantidade de procedimentos de TAVI realizados. Baseado no pressuposto de realização de um máximo de 80 procedimentos por mês no Brasil, foi estimado um impacto em torno de 78 milhões de reais no primeiro ano e um impacto total, em 5 anos, de aproximadamente 467 milhões de reais. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram realizadas pesquisas nos bancos de dados de ensaios clínicos e patentes Clinical Trials , Cortellis , ECRI, Espacenet e Patentscope e no site do FDA. Para isto, foram utilizados os descritores "severe aortic stenosis" e "aortic stenosis". Dentre os resultados obtidos foram desconsiderados os implantes que já são comercializados no mercado do brasileiro, de modo a proporcionar uma melhor prospecção de mercado. Foi identificado um TAVI registrado no FDA e quatro pedidos patentários internacionais que possuem depósito brasileiro, contudo devido a sua recente inclusão internacional ainda não possui pedido em fase nacional. CONSIDERAÇÕES FINAIS: A principal vantagem do TAVI é permitir a troca valvar aórtica sem a necessidade de toracotomia ou circulação extracorpórea, o que o coloca como opção terapêutica para pacientes com estenose aórtica inoperáveis. Demanda expertise médica e estrutura hospitalar com suporte de sala de hemodinâmica e cirurgia cardíaca. O controle na qualidade do atendimento e no impacto orçamentário estão diretamente relacionados a quantidade de centros e de procedimentos por centro que poderão ser autorizados para realização do TAVI. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Pelo exposto, os membros da Conitec, em sua 95ª reunião ordinária, no dia 04 de março de 2021, recomendaram por unanimidade, a não incorporação no SUS do TAVI para tratamento de pacientes com estenose aórtica grave inoperáveis. Considerou-se que, apesar das evidências que suportam o benefício clínico da intervenção, os dados econômicos de relação de custo-utilidade incremental e impacto orçamentário são desfavoráveis. A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: A Consulta Pública nº 15/2021 foi realizada entre os dias 18/03/2021 e 06/04/2021. Foram recebidas 17 contribuições, sendo 12 pelo formulário para contribuições técnico-científicas e cinco pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. RECOMENDAÇÃO FINAL: Pelo exposto, o Plenário da Conitec, em sua 96ª Reunião Ordinária, no dia 05 de maio de 2021, deliberou por unanimidade recomendar a incorporação do implante percutâneo da válvula aórtica (TAVI) para tratamento da estenose aórtica grave em pacientes com estenose aórtica grave sintomática inoperáveis. Os membros da Conitec consideraram o benefício clínico com ganhos em sobrevida e qualidade de vida dos pacientes para recomendar a incorporação desta tecnologia que está condicionada, no máximo, ao valor considerado custo-efetivo na análise para o Sistema Único de Saúde (SUS). Assim, foi assinado o Registro de Deliberação nº 606/2021. DECISÃO: Incorporar o implante percutâneo de válvula aórtica (TAVI) para tratamento da estenose aórtica grave em pacientes inoperáveisno âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria nº 32, republicada no Diário Oficial da União nº 123, Seção 1, página 195, em 02 de julho de 2021.

Cardiac Rehabilitation for Transcatheter Aortic Valve Replacement.

More than 300,000 patients worldwide have undergone transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). The rise in TAVR as a treatment option is driven in large part by evidence showing its benefits compared with medical treatment in patients with symptomatic severe AS who were too ill to undergo surgical aortic valve replacement. Cardiac rehabilitation (CR) is recommended after valvular cardiac surgery for improving exercise capacity, with data also now showing its utility to improve quality of life, moderate frailty, and increase survival. This review describes the state of the art of CR for TAVR.

Relation of Postdischarge Care Fragmentation and Outcomes in Transcatheter Aortic Valve Implantation from the STS/ACC TVT Registry.

Fragmented care following elective surgery has been associated with poor outcomes. The association between fragmented care and outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) is unknown. We examined patients who underwent TAVI from 2011 to 2015 at 374 sites in the STS/ACC TVT Registry, linked to Center for Medicare and Medicaid Services claims data. Fragmented care was defined as at least one readmission to a site other than the implanting TAVI center within 90 days after discharge, whereas continuous care was defined as readmission to the same implanting center. We compared adjusted 1-year outcomes, including stroke, bleeding, heart failure, mortality, and all-cause readmission in patients who received fragmented versus continuous care. Among 8,927 patients who received a TAVI between 2011 and 2015, 27.4% were readmitted within 90 days of discharge. Most patients received fragmented care (57.0%). Compared with the continuous care group, the fragmented care group was more likely to have severe chronic lung disease, cerebrovascular disease, and heart failure. States that had lower TAVI volume per Center for Medicare and Medicaid Services population had greater fragmentation. Patients living > 30 minutes from their TAVI center had an increased risk of fragmented care 1.07 (confidence interval [CI] 1.06 to 1.09, p < 0.001). After adjustment for comorbidities and procedural complications, fragmented care was associated with increased 1-year mortality (hazards ratio 1.18, CI 1.04 to 1.35, p = 0.010) and all-cause readmission (hazards ratio 1.08, CI 1.00 to 1.16, p = 0.051. In conclusion, fragmented readmission following TAVI is common, and is associated with increased 1-year mortality and readmission. Efforts to improve coordination of care may improve these outcomes and optimize long-term benefits yielded from TAVI.

Exercise Training Has Contrasting Effects in Myocardial Infarction and Pressure Overload Due to Divergent Endothelial Nitric Oxide Synthase Regulation.

The beneficial effects of exercise training (EX) on cardiac pathology are well recognized. Previously, we found that the effects of EX on cardiac dysfunction in mice critically depend on the underlying etiology. EX exerted beneficial effects after myocardial infarction (MI); however, cardiac pathology following pressure overload produced by transverse aortic constriction (TAC) was aggravated by EX. In the presented study, we investigated whether the contrasting effects of EX on cardiac dysfunction can be explained by an etiology-specific response of endothelial nitric oxide (NO) synthase (eNOS) to EX, which divergently affects the balance between nitric oxide and superoxide. For this purpose, mice were exposed to eight weeks of voluntary wheel running or sedentary housing (SED), immediately after sham, MI, or TAC surgery. Left ventricular (LV) function was assessed using echocardiography and hemodynamic measurements. EX ameliorated LV dysfunction and remodeling after MI, but not following TAC, in which EX even aggravated fibrosis. Strikingly, EX attenuated superoxide levels after MI, but exacerbated NOS-dependent superoxide levels following TAC. Similarly, elevated eNOS S-glutathionylation and eNOS monomerization, which were observed in both MI and TAC, were corrected by EX in MI, but aggravated by EX after TAC. Additionally, EX reduced antioxidant activity in TAC, while it was maintained following EX in MI. In conclusion, the present study shows that EX mitigates cardiac dysfunction after MI, likely by attenuating eNOS uncoupling-mediated oxidative stress, whereas EX tends to aggravate cardiac dysfunction following TAC, likely due to exacerbating eNOS-mediated oxidative stress.

The JUPITER registry: 1-year results of transapical aortic valve implantation using a second-generation transcatheter heart valve in patients with aortic stenosis.

OBJECTIVES: Transcatheter aortic valve replacement (TAVR) is an established therapy for patients with aortic stenosis (AS) at high surgical risk. The JenaValve™ is a second-generation, self-expanding transcatheter heart valve (THV), implanted through transapical access (TA). During stent deployment, a specific 'clipping-mechanism' engages native aortic valve cusps for fixation. We present 1-year outcomes of the JUPITER registry, a post-market registry of the JenaValve for TA-TAVR. METHODS: The JUPITER registry is a prospective, multicentre, uncontrolled and observational European study to evaluate the long-term safety and effectiveness of the Conformité Européenne-marked JenaValve THV. A total of 180 patients with AS were enrolled between 2012 and 2014. End-points were adjudicated in accordance with the valve academic research consortium document no. 1 definitions. RESULTS: The mean age was 80.4 ± 5.9 years and the mean logistic European system for cardiac operative risk evaluation I 21.2 ± 14.7%. The procedure was successful in 95.0% (171/180), implantation of a second THV (valve-in-valve) was performed in 2.2% (4/180) and conversion to surgical aortic valve replacement (SAVR) was necessary in 2.8% (5/180). No annular rupture or coronary ostia obstruction occurred. Two patients required SAVR after the day of index procedure (1.1%). All-cause mortality at 30 days was 11.1% (20/180), being cardiovascular in 7.2% (13/180). A major stroke occurred in 1.1% (2/180) at 30 days, no additional major strokes were observed during 1 year. All-cause mortality after 30 days was 13.1% (21/160) and combined efficacy at 1 year was 80.8% (122/151). At 1-year follow-up, no patient presented with more than moderate paravalvular leakage, while 2 patients (3.2%) showed moderate, 12 (19.0%) mild and 49 (82.4%) trace/none paravalvular regurgitation. CONCLUSIONS: In a high-risk cohort of patients undergoing TA-TAVR for AS, the use of the JenaValve THV is safe and effective. In patients at higher risk for coronary ostia obstruction, annular rupture or with limited aortic valve calcification, the JenaValve might be preferable for implantation due to its clipping-mechanism engaging native aortic valve cusps for fixation with reduced radial forces of the self-expanding stent.

Conventional aortic valve replacement for high-risk aortic stenosis patients not suitable for trans-catheter aortic valve implantation: feasibility and outcome.

OBJECTIVE: High-risk patients with aortic stenosis are increasingly referred to specialist multidisciplinary teams (MDTs) for consideration of trans-catheter aortic valve implantation (TAVI). A subgroup of these cases is unsuitable for TAVI, and high-risk conventional aortic valve replacement (AVR) is undertaken. We have studied our outcomes in this cohort. METHODS: Data prospectively collected between March 2008 and November 2009 for patients (n = 28, nine male) undergoing high-risk AVR were analysed. The mean age was 78.4 ± 9.2 years. The mean additive EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 10.0 ± 3.6 and mean logistic EuroSCORE was 19.9 ± 18.8. Three patients had undergone previous coronary artery bypass grafting (CABG). RESULTS: The mean ejection fraction was 51 ± 16%, mean valve area 0.56 ± 0.19 cm², and mean peak gradient 91 ± 27 mm Hg. Ascending aortic, right axillary artery and femoral artery cannulation was used in 64%, 29% and 7% of cases, respectively. Median cross-clamp and cardiopulmonary bypass times were 84 (68-143) min and 111 (94-223) min. The median (range) inserted valve size was 21 (19-25) mm. Median intensive care and overall hospital stay were 5 (2-37) and 11 (5-44) days, respectively. In-hospital mortality was 4% (one patient). Postoperative complications included re-operation for bleeding (7%), renal failure (21%), tracheostomy (14%), sternal wound infection (7%), atrial fibrillation (25%) and permanent pacemaker implantation (7%). Kaplan-Meier survival at median follow-up of 359 (148-744) days was 81% (one further death of non-cardiac aetiology). Quality-of-life assessment at follow-up also yielded satisfactory results. CONCLUSIONS: MDT assessment of high-risk aortic stenosis in the era of TAVI has increased the number of referrals. Conventional open surgery remains a valid option for these patients, with acceptable in-hospital mortality and early/midterm outcomes but high in-hospital morbidity.

The effect of moderate exercise training on oxygen uptake post-aortic/mitral valve surgery.

BACKGROUND: This study determined the response of aortic and/or mitral valve replacement/reconstruction (AVR/MVR) surgery patients to a 3-month exercise rehabilitation program (ERP) of moderate intensity, frequency, and duration that commenced approximately 9 weeks post-operatively. METHODS: Based on geographic proximity and availability of transportation to attend ERP classes, 29 experimental subjects were enrolled in the ERP and 20 control subjects received standard care that did not include the ERP, but did not prohibit activity/exercise. Exercise tolerance was determined from estimated oxygen uptake (VO2) during exercise tolerance testing (GXT) before and after standard care or the ERP. RESULTS: VO2 at the maximum stage of the GXT increased significantly (P < or = 05) for the experimental (4.89 +/- 5.07 mL/kg/min) and control (5.11 +/- 4.48 mL/kg/min) groups. No significant between-group differences were noted in VO2 at the maximum stage of the exercise testing or at the target heart rate (HR). Furthermore, reported exercise levels of subjects in both groups were comparable and sufficient for training effects to occur. CONCLUSION: Alternate strategies to improve exercise tolerance such as home-based rehabilitation programs should be investigated for relatively healthy aortic and/or mitral valve surgical patients.

Twenty-four years' implant duration of the aortic Starr-Edwards Silastic ball prosthesis: a valve of the past?

Six years after the first aortic valve replacement with the Starr-Edwards Silastic ball prosthesis at Oregon Health Sciences University, the model 1260 was implanted in a 44-year-old patient at our department. During 24 years no signs of dysfunction, thromboembolism, thrombosis, periprosthetic leaks or hemolysis were observed. Material test showed no signs of fatigue. The dimension of the Silastic poppet was found to be one millimeter less than the original specifications of these poppets and there were some lipid infiltrations. Functionally the poppet was found to be nonvariant. Histologic findings detected focal hyalinization and giant cells without signs of acute inflammation or ulceration. With regard to its reliability and durability, the Starr-Edwards valve prosthesis should not be viewed with disfavor.

Exercise tolerance and working capacity after valve replacement.

Between 1978 and 1987, 1270 patients who survived single aortic or mitral valve replacement at the Rehabilitation Center in Bad Krozingen, Germany, underwent a comprehensive rehabilitation program. The preoperative diagnosis was isolated aortic stenosis in 425, isolated aortic regurgitation in 159, mixed aortic lesion in 211, isolated mitral stenosis in 208, isolated mitral insufficiency in 137 and mixed mitral lesion in 130 cases. Follow up examinations were carried out one and six months after surgery, and at yearly intervals thereafter. Exercise testing was performed with an electrically braked bicycle ergometer in the supine position, and the load was increased by 25 or 50 watts every two minutes until fatigue, severe angina, more than 0.3 mV ST-segment depression, or 80% of the age predicted maximum heart rate was achieved. Patients after aortic valve replacement had a better exercise performance one month after operation than did those after mitral valve replacement. Those with mitral stenosis showed more severe impairment of exercise tolerance than did the mitral insufficiency group. There was a steady increase in exercise tolerance between one and six months postoperatively, both in patients with aortic and those with mitral valve replacement, but the difference in performance between the two groups was still present (72% versus 57% of normal). The results of univariate and multivariate analyses showed that the preoperative employment status was the most important factor for postoperative return to work, followed by gender (male > female), exercise tolerance and valualar lesion (aortic > mitral).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic valve replacement in octogenarians.

In a consecutive series of 1109 patients undergoing aortic valve replacement (AVR) between January 1988 and December 1990, there were 48 patients (33 female, 15 male) over 80 years of age (mean age 83.5 years, median 82.9 years). Of those, 33 had aortic stenosis and 15 combined aortic valve disease, with additional coronary artery disease being present in 36. Isolated AVR was performed in 25 patients, and it was combined with coronary venous bypass grafting, with 1-4 (mean 1.8) peripheral anastomoses in 23. Two patients died within 30 days (early mortality 4.2%). Non-fatal complications included one hemiparesis, four transient cerebral disorders, two cases of pneumonia which led to ventilatory assistance, three rethoracotomies because of postoperative bleeding, 15 tachycardias and one transient AV block. Late results were obtained after a median follow up time of 22 months. There were eight late deaths (four cardiac related, four not related) and a low incidence of non-fatal complications (two episodes of gastrointestinal bleeding while on oral anticoagulation, one cerebral transient ischemic attack and one acute left ventricular failure). Nine patients are in NYHA Class I, 12 in Class I-II, 11 in Class II, three in Class II-III and three in Class III. Of the surviving 38 patients, four are currently living in a home for the aged or a nursing home, while all the others are living in their own homes and are able to sustain a relatively independent life-style. We conclude that in very old patients with aortic valve disease, AVR can be performed with low mortality and few non-fatal complications.

[Evaluation of patient rehabilitation effectiveness after aortic valve prosthesis based on spiroergometric study data]. / Otsenka éffektivnosti reabilitatsii bol'nykh posle protezirovaniia aortal'nogo kaplana po dannym spiroérgometricheskogo issledovaniia.

Patients after surgery introducing aortal valve prosthesis in cases of rheumatic aortal defect or defect due to bacterial endocarditis were examined using spiro- and bicycle ergometry. Two groups of patients were compared: those subjected to rehabilitation procedures and a control group undergoing no rehabilitation program. Functional results were better in post-rehabilitation patients. By the end of the rehabilitation program, the examined spiroergometric parameters were significantly closer to those of normal subjects, as compared to the controls. Spiroergometric investigation in patients with newly applied aortal valve prostheses supplements clinical data in providing a more profound functional evaluation of surgical results and rehabilitation efficiency.