Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCbnV5SrFGhkJP4V5JWXQjpStS0066-782X201900120111210.36660/abc.20190753Short EditorialImpact of Transcatheter Aortic Valve Implantation on Kidney Function: the “Renovalvular” Interaction in Aortic Stenosis0000-0002-2720-8595SantisAntonio deUniversidade de São PauloInstituto do CoraçãoUnidade Clinica de ValvopatiaCuritibaPRBrazilUniversidade de São Paulo Instituto do Coração - Unidade Clinica de Valvopatia, São Paulo, SP - BrazilMailing Address: Antonio de Santis, Av. Dr. Eneas Carvalho de Aguiar, 44. Postal Code 05403-000, São Paulo, SP - Brazil E-mail: antonio.slopes@einstein.br2122019122019113611121113This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.KeywordsHeart Failure/complicationsRenal Insufficiency/ complicationsAortic Valve Stenosis/complicationsTranscatheter Aortic Valve Replacement/trendsRisk Assessment
The advent of renal congestion in heart failure was first described by Frédéric Justin Collet (1870-1966), a French pathologist who found the notion of passive renal congestion related to heart dysfunction, creating the revealing term “rein cardiaque” in the early 1900s.1 The term cardiorenal syndrome emerged from a 2004 National Heart, Lung, and Blood Institute Working GrouP conference evaluating the complex interactions between the heart and kidney.2 The main pathophysiological mechanisms related to this condition are increased central venous and intra-abdominal pressures; reduced cardiac output and cardiac index; neurohormonal dysregulation; oxidative stress and inflammatory mediators.3 Degenerative aortic stenosis (AS) represents one of the most prevalent valvular heart diseases and an important cause of heart failure, with a strong correlation with aging process. The combination of atherosclerosis, biomineralization and oxidative stress leads to calcium deposition within the valve leaflets.4 The “renovalvular” interaction in AS may represent a two-way path, from a pathophysiological perspective. In one way, AS may impair kidney function by arterial hypoperfusion and systemic venous congestion. On the other way, chronic kidney disease (CKD) is also an important risk factor for AS, due to the massive and aggressive calcification of the leaflets, mainly imposed by imbalances in the calcium and phosphorus homeostasis.5
For patients with AS undergoing conventional surgical aortic valve replacement (AVR), there is an increase in complication rates such as major bleeding and reoperation when comparing patients with moderately reduced kidney function (estimated glomerular filtration rate [eGFR] between 30-60 ml/min/1.73 m2) versus those without kidney disease.6 Mortality after surgical AVR also increases with worsening GFR.7
The development of the transcatheter aortic valve replacement (TAVR) for the treatment of AS has brought hope for a grouP of patients without effective therapeutic perspective due to their clinical profile, characterized by the presence of clinical frailty and multiple comorbidities, making surgical AVR not feasible.8 In this scenario, TAVR represents a potentially less invasive therapeutic alternative for patients with AS and CKD. Some previous studies evaluated the clinical impact of TAVR on patients with CKD. In the classical PARTNER trial, there was a 34.4% 1-year mortality for patients with severe CKD.9 For patients undergoing dialysis treatment and TAVR, there was also a higher mortality rate and major bleeding.10 Moreover, the occurrence of acute kidney injury in the peri-procedural TAVR period is also associated with poor outcomes.11 On the other hand, some previous studies demonstrate a positive impact of TAVR on renal function, especially in patients with moderate to severe CKD, with a significant recovery of eGFR possible related to the improvement of cardiac output and reduction of systemic venous congestion.12-14
Promisingly, the present study conducted by Calça et al.,15 provides additional data on the positive impact of TAVR on the kidney function. Through a retrospective and unicentric study, 233 patients with AS who underwent TAVR were stratified into 3 groups according to basal eGFR (ml/min/1.73 m2): grouP 1 (eGFR > 60), grouP 2 (30 ≤ eGFR < 60) and grouP 3 (eGFR < 30). The renal function was re-accessed one month and one year after TAVR. The authors observed a significant improvement in eGFR in patients with moderate (grouP 2) to severe (grouP 3) CKD (around 15.6% in one year; around 58.6% in one year, respectively). Conversely, patients from grouP 1 had a progressive decline in eGFR one year after the TAVR procedure (P < 0.001 vs. pre-TAVR). Nevertheless, there was a low incidence of dialysis therapy in one year (2.4%). Possible reasons implicated by the authors in this worsening of eGFR in grouP 1 were higher use of iodinated contrast in this grouP (65% of patients) and the use of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in the post-procedure period. Multivariate logistic regression analysis identified that the use of iodinated contrast was an independent predictor of worsening kidney function, unrelated to the volume of contrast used.
Despite its inherent limitations (single center, retrospective and observational study) the study by Calça et al.15 brings a promising light on the impact of TAVR on kidney function in patients with moderate to severe CKD. This pre-procedure kidney dysfunction may not be an exclusion issue for the TAVR, given to the possibility of short- and medium-term improvement. Future randomized, multicenter studies, with a stricter contrast type control and longer, follow uP , are required for a definitive conclusion.
Short Editorial related to the article: Impact of Transcatheter Aortic Valve Implantation on Kidney Function
References1 Collet FJ. Précis de pathologie interne. Paris: Gaston Doin & Cie;1930. P . 653-667.ColletFJPrécis de pathologie interneParis: Gaston Doin & Cie19306536672 Cardio-Renal Connections in Heart Failure and Cardiovascular Disease. Bethesda: National Heart, Lung, and Blood Institute (NHLBI); 2004.Cardio-Renal Connections in Heart Failure and Cardiovascular DiseaseBethesdaNational Heart, Lung, and Blood Institute (NHLBI)20043 Kumar U, Wettersten N, Garimella PS. Cardiorenal Syndrome: Pathophysiology. Cardiol Clin. 2019;37(3):251-65.KumarUWetterstenNGarimellaPSCardiorenal Syndrome: PathophysiologyCardiol Clin20193732512654 Liberman M, Bassi E, Martinatti MK, Lario FC, Wosniak J Jr, Pomerantzeff PM, Laurindo FR. Oxidant generation predominates around calcifying foci and enhances progression of aortic valve calcification. Arterioscler Thromb Vasc Biol. 2008;2(3):463-70.LibermanMBassiEMartinattiMKLarioFCWosniakJJrPomerantzeffPMLaurindoFROxidant generation predominates around calcifying foci and enhances progression of aortic valve calcificationArterioscler Thromb Vasc Biol2008234634705 Ternacle J, Côté N, Krapf L, Nguyen A, Clavel MA, Pibarot P . Chronic kidney disease and the pathophysiology of valvular heart disease. Can J Cardiol.2019;35(9):1195-207.TernacleJCôtéNKrapfLNguyenAClavelMAPibarotPChronic kidney disease and the pathophysiology of valvular heart diseaseCan J Cardiol2019359119512076 Aljohani S, Alqahtani F, Almustafa A, Boobes K, Modi S, AlkhouLI M. Trends and outcomes of aortic valve replacement in patients with end-stage renal disease on hemodialysis. Am J Cardiol. 2017;120(9):1626-32.AljohaniSAlqahtaniFAlmustafaABoobesKModiSAlkhouLIMTrends and outcomes of aortic valve replacement in patients with end-stage renal disease on hemodialysisAm J Cardiol20171209162616327 Thourani VH, Forcillo J, Beohar N, Doshi D, Parvataneni R, Ayele GM, et al. Impact of preoperative chronic kidney disease in 2,531 high-risk and inoperable patients undergoing transcatheter aortic valve replacement in the PARTNER Trial. Ann Thorac Surg. 2016;102(4):1172-80.ThouraniVHForcilloJBeoharNDoshiDParvataneniRAyeleGMImpact of preoperative chronic kidney disease in 2,531 high-risk and inoperable patients undergoing transcatheter aortic valve replacement in the PARTNER TrialAnn Thorac Surg20161024117211808 Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. N Engl J Med. 2010;363(17):1597-607.LeonMBSmithCRMackMMillerDCMosesJWSvenssonLGTranscatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo SurgeryN Engl J Med201036317159716079 Glaser N, Jackson V, Holzmann MJ. Late survival after aortic valve replacement in patients with moderately reduced kidney function. J Am Heart Assoc. 2016;5(12):pii e004287.GlaserNJacksonVHolzmannMJLate survival after aortic valve replacement in patients with moderately reduced kidney functionJ Am Heart Assoc2016512e00428710 SzerliP MZ, Zajarias A, VemalapalLI S, Brennan M, Dai D, Maniar H, et al. Transcatheter aortic valve replacement in patients with end-stage renal disease. J Am Coll Cardiol. 2019;73(22):2806-15.SzerliPMZZajariasAVemalapalLISBrennanMDaiDManiarHTranscatheter aortic valve replacement in patients with end-stage renal diseaseJ Am Coll Cardiol201973222806281511 Elhmidi Y, Bleiziffer S, Deutsch MA,Krane M, MazzitelLI D, Piazza N. Acute kidney injury after transcatheter aortic valve implantation: incidence, predictors and impact on mortality. Arch Cardiovasc Dis. 2014;107(2):133-9.ElhmidiYBleizifferSDeutschMAKraneMMazzitelLIDPiazzaNAcute kidney injury after transcatheter aortic valve implantation: incidence, predictors and impact on mortalityArch Cardiovasc Dis2014107213313912 Faillace BLR, Ribeiro HB, Campos CM, Truffa AAM, Bernardi FL, Oliveira MDP , et al. Potential of transcatheter aortic valve replacement to improve post-procedure renal function. Cardiovasc Revascularization Med. 2017;18(7):507-11.FaillaceBLRRibeiroHBCamposCMTruffaAAMBernardiFLOliveiraMDPPotential of transcatheter aortic valve replacement to improve post-procedure renal functionCardiovasc Revascularization Med201718750751113 Azarbal A, Malenka DJ, Huang Y-L, Ross CS, Solomon RJ, DeVries JT, et al. Recovery of kidney disfunction after transcatheter aortic valve implantation (from the Northern New England Cardiovascular Disease Study GrouP ). Am J Cardiol. 2018;123(1):426-33.AzarbalAMalenkaDJHuang Y-LRossCSSolomonRJDeVriesJTRecovery of kidney disfunction after transcatheter aortic valve implantation (from the Northern New England Cardiovascular Disease Study GrouP )Am J Cardiol2018123142643314 Najjar M, Yerebakan H, Sorabella RA, Guglielmetti L, Vandenberge J, Kurlansky P , et al. Reversibility of chronic kidney disease and outcomes following aortic valve replacement. Interact Cardiovasc Thorac Surg. 2015;21(4):499-505.NajjarMYerebakanHSorabellaRAGuglielmettiLVandenbergeJKurlanskyPReversibility of chronic kidney disease and outcomes following aortic valve replacementInteract Cardiovasc Thorac Surg201521449950515 Calça R, Teles RC, Branco P , Gaspar A, Brito J, Nolasco T et al. Impact of Transcatheter Aortic Valve Implantation on Kidney Function. Arq Bras Cardiol. 2019; 113(6):1104-1111CalçaRTelesRCBrancoPGasparABritoJNolasco T et alImpact of Transcatheter Aortic Valve Implantation on Kidney FunctionArq Bras Cardiol2019113611041111MinieditorialImpacto do Implante da Válvula Aórtica Transcateter na Função Renal: A Interação “Renovalvular” na Estenose Aórtica0000-0002-2720-8595SantisAntonio deUniversidade de São Paulo Instituto do Coração - Unidade Clinica de Valvopatia, São Paulo, SP - BrasilCorrespondência: Antonio de Santis, Av. Dr. Eneas Carvalho de Aguiar, 44. CEP 05403-000, São Paulo, SP - Brasil E-mail: antonio.slopes@einstein.brPalavras-chaveInsuficiência Cardíaca/complicaçõesInsuficiência Renal/ complicaçõesEstenose da Valva Aórtica/complicaçõesSubstituição da Valva Aórtica Transcateter/tendências, Medição de Risco
O advento da congestão renal na insuficiência cardíaca foi descrito pela primeira vez por Frédéric Justin Collet (1870-1966), um patologista francês que descobriu a noção de congestão renal passiva relacionada à disfunção cardíaca, criando o termo revelador "rein cardiaque" no início de 1900.1 O termo ‘síndrome cardiorrenal’ surgiu em uma conferência do National Heart, Lung, and Blood Institute Working GrouP de 2004, avaliando as complexas interações entre coração e rim.2 Os principais mecanismos fisiopatológicos relacionados a essa condição são o aumento das pressões venosas centrais e intra-abdominais; débito cardíaco e índice cardíaco reduzidos; desregulação neuro-hormonal; estresse oxidativo e mediadores inflamatórios.3 A estenose aórtica (EA) degenerativa representa uma das doenças cardíacas valvares mais prevalentes e uma causa importante de insuficiência cardíaca, tendo forte correlação com o processo do envelhecimento. A combinação de aterosclerose, biomineralização e estresse oxidativo leva à deposição de cálcio nos folhetos valvares.4 A interação “renovalvular” na EA pode representar um caminho de mão dupla, de uma perspectiva fisiopatológica. Por um lado, a EA pode prejudicar a função renal pela hipoperfusão arterial e congestão venosa sistêmica. Por outro lado, a doença renal crônica (DRC) também é um importante fator de risco para EA, devido à calcificação maciça e agressiva dos folhetos, imposta principalmente por desequilíbrios na homeostase do cálcio e fósforo.5
Para pacientes com EA submetidos à substituição da válvula aórtica (SVA) cirúrgica convencional, há um aumento nas taxas de complicações, como sangramento maior e reoperação, em comparação com pacientes com função renal moderadamente reduzida (taxa de filtração glomerular estimada [TFGe] entre 30-60 mL/min/1,73 m2) versus aqueles sem doença renal.6 A mortalidade após a SVA cirúrgica também aumenta com o agravamento da TFG.7
O desenvolvimento da substituição da válvula aórtica transcateter (TAVR, sigla do inglês transcatheter aortic valve replacement) para o tratamento da EA trouxe esperança para um grupo de pacientes sem perspectiva terapêutica efetiva devido ao seu perfil clínico, caracterizado pela presença de fragilidade clínica e múltiplas comorbidades, impossibilitando a SVA cirúrgica.8 Nesse cenário, a TAVR representa uma alternativa terapêutica potencialmente menos invasiva para pacientes com EA e DRC. Alguns estudos anteriores avaliaram o impacto clínico da TAVR em pacientes com DRC. No clássico estudo PARTNER, houve uma mortalidade de 34,4% em 1 ano para pacientes com DRC grave.9 Para pacientes em tratamento dialítico e TAVR, também houve uma maior taxa de mortalidade e sangramento maior.10 Além disso, a ocorrência de lesão renal aguda no período peri-procedimento da TAVR também está associada a prognósticos ruins.11 Por outro lado, alguns estudos anteriores demonstram um impacto positivo da TAVR na função renal, principalmente em pacientes com DRC moderada a grave, com recuperação significativa da TFGe, possivelmente relacionada à melhora do débito cardíaco e redução da congestão venosa sistêmica.12-14
De maneira promissora, o presente estudo realizado por Calça et al.,15 fornece dados adicionais sobre o impacto positivo da TAVR na função renal. Através de um estudo retrospectivo e unicêntrico, 233 pacientes com EA submetidos a TAVR foram estratificados em 3 grupos de acordo com a TFGe basal (mL/min/1,73 m2): grupo 1 (TFGe > 60), grupo 2 (30 ≤ TFGe < 60) e grupo 3 (TFGe < 30). A função renal foi reavaliada novamente um mês e um ano após a TAVR. Os autores observaram uma melhora significativa na TFGe em pacientes com DRC moderada (grupo 2) a grave (grupo 3) (cerca de 15,6% em um ano; cerca de 58,6% em um ano, respectivamente). Por outro lado, os pacientes do grupo 1 apresentaram um declínio progressivo na TFGe um ano após o procedimento de TAVR (P < 0,001 vs. pré-TAVR). No entanto, houve uma baixa incidência de terapia dialítica em um ano (2,4%). As possíveis razões consideradas pelos autores para esse agravamento da TFGe no grupo 1 foram o maior uso de contraste iodado nesse grupo (65% dos pacientes) e o uso de bloqueadores dos receptores da angiotensina e inibidores da enzima de conversão da angiotensina no período pós-procedimento. A análise de regressão logística multivariada identificou que o uso de contraste iodado foi um preditor independente de agravamento da função renal, não relacionado ao volume de contraste utilizado.
Apesar de suas limitações inerentes (centro único, estudo retrospectivo e observacional), o estudo de Calça et al.15 traz uma luz promissora sobre o impacto da TAVR na função renal em pacientes com DRC moderada a grave. Essa disfunção renal pré-procedimento pode não ser um questão de exclusão para a TAVR, dada a possibilidade de melhora a curto e médio prazo. Futuros estudos randomizados, multicêntricos, com um controle do tipo de contraste mais rigoroso e acompanhamento mais longo, são necessários para uma conclusão definitiva.
Minieditorial referente ao artigo: Impacto do Implante Percutâneo de Válvula Aórtica na Função Renal