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CONVULSÃO E EPILEPSIA Profa Rebeca Bacchi DEFINIÇÃO E FISIOPATOLOGIA ✔ Manifestação clínica de descargas neuronais excessivas no córtex cerebral ✔ Período clínico de comportamento anormal, causado por uma descarga elétrica, paroxística, descontrolada e transitória, nos neurônios cere...

CONVULSÃO E EPILEPSIA Profa Rebeca Bacchi DEFINIÇÃO E FISIOPATOLOGIA ✔ Manifestação clínica de descargas neuronais excessivas no córtex cerebral ✔ Período clínico de comportamento anormal, causado por uma descarga elétrica, paroxística, descontrolada e transitória, nos neurônios cerebrais. DEFINIÇÃO E FISIOPATOLOGIA – Comprometimento ou perda de consciência episódicos; – Fenômenos motores anormais; – Distúrbios psíquicos ou sensoriais; – Sinais nervosos autônomos: salivação, vômito, micção e defecção. INIBIÇÃO NEURONAL INADEQUADA E/OU EXCITAÇÃO NEURONAL EXCESSIVA LIMIAR DE EXCITABILIDADE  Convulsão focal / Convulsão Convulsão generalizada generalizada focal secundária  Tipos de Convulsão ✔ TÔNICAS Rigidez muscular generalizada. ✔ CLÔNICAS Movimentos de extensão e contração. ✔ CONVULSÕES ATÔNICAS Perda repentina do tônus muscular. ✔ CONVULSÕES MIOCLÔNICAS Breves contrações generalizadas ou restritas a grupos musculares individuais. AURA – Pré-Ictal ICTO PÓS-ICTAL PÓS-ICTAL GENERALIZADA TÔNICO-CLÔNICA COMPORTAMENTOS BIZARROS ✔ Caçar moscas ✔ Morder a cauda CONSULSÃO X ✔ Mamar o flanco SÍNCOPE FASES  Conceitos ✔ Cluster: dois ou mais ataques convulsivos que ocorrem dentro de 24 horas. ✔ Status epilepticus: atividade convulsiva contínua que dura mais de 10 minutos ou séries múltiplas de ataques convulsivos sem recuperação da função neurológica basal entre os episódios. ✔ Epilepsia: doença neurológica crônica caracterizada por ataques convulsivos recorrentes.  EPILEPSIA ✔ DEFINIÇÃO Síndrome caracterizada por episódios convulsivos recidivantes de origem intracraniana ✔ TIPOS Primária ou idiopática Secundária ou adquirida  ETIOLOGIAS INTRACRANIANAS – infecciosas –inflamatórias –neoplasias –má formações (distúrbios congênitos) –traumática –tóxica –vascular  ETIOLOGIAS EXTRACRANIANAS – hipoglicemia – hipóxia –Encefalopatia hepática / urêmica –Parasitismo –Hipocalcemia –hiperlipoproteinemia ✔Extracranianas ✔Intracranianas ✔Idiopáticas ✔Extracranianas ✔Intracranianas ✔Idiopáticas ✔Extracranianas ✔Intracranianas ✔Idiopáticas ✔Extracranianas ✔Intracranianas ✔Idiopáticas ✔Extracranianas ✔Intracranianas o Doenças degenerativas ✔Idiopáticas o Hidrocefalia o Neoplasias o Doenças infecciosas/inflamatórias o Traumatismos o Doença isquêmica/vascular  EPILEPSIA IDIOPÁTICA Poodle, PA, Begale, Dacsh., ✔ Cães Husky, Setter, Collie, São ✔ Hereditária B., Cocker, Dálm., Lab. e ✔ Idade: 1 a 5 anos de idade Golden ✔ Convulsões tônico-clônico generalizadas ✔ Exames normais ✔ Ausência de sinais clínicos no período inter-ictal  EPILEPSIA ADQUIRIDA ✔ Lesões cranianas ✔ Exames físico, neurológico e complementares anormais  ABORDAGEM DIAGNÓSTICA TEM QUE RESPONDER 2 PERGUNTAS 1.O que o paciente tem é realmente convulsão? 2. Se sim, qual a causa?  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔ Resenha – raça – idade  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔ < 1 ano Doenças do desenvolvimento Tóxica Infecciosa Metabólica Nutricional Traumática  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔ 1 a 5 anos... Epilepsia idiopática  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔ > 5 anos... Metabólica Neoplásica Vascular  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔ Anamnese – Descreva-me o que observou? Antes, durante e depois ? – Além do “ocorrido”, viu algo anormal? – Quando e com o que foi vacinado? – Como é o ambiente (agentes tóxicos)? – Quais problemas ou doença que já teve? – Histórico familiar (pais e irmãos ninhada)  DIAGNÓSTICO DO PACIENTE CONVULSIVO ✔Exame físico / neurológico – Normal – epilepsia idiopática – Anormal – lesão funcional ou estrutural EXAMES COMPLEMENTARES Hemograma, bioquímicos, urinálise Análise do LCR Sorologia / PCR Eletroencefalografia (EEG) EXAMES COMPLEMENTARES Diagnóstico por imagem Radiografia crânio?!?! Tomografia computadorizada Ressonância magnética  TRATAMENTO ✔ OBJETIVOS ✔ FÊMEAS  QUANDO TRATAR? ✔ Quando iniciar: 2 crises, intervalo < 6-8 semanas, cãe com epilepsia idiopática < 2 anos, cães com crises agrupadas ✔ Quando não iniciar? Intervalo > 8 semanas ✔ Quando descontinuar? Tentar > 1 ano livre – NUNCA EM CÃES COM EPILEPSIA IDIOPÁTICA  Medicamentos que ⇓ limiar convulsivo ✔Acepromazina ✔Estrógeno ✔Xilazina ✔Anti-depressivos ✔Quetamina ✔Broncodilatadores ✔Metoclopramida ✔Corticosteróides ANTICONVULSIVANTES X  FENOBARBITAL ✔ 2,5 mg /kg/BID ✔ ESTABILIZAÇÃO SÉRICA – 2 a 3 semanas ✔ EFEITOS COLATERAIS  FENOBARBITAL ✔ MONITORAR ✔ Nova dose = dose (mg/dia) x [ ] sérica desejada [ ] sérica mensurada ✔ 45, 90, 180 e 360 dias – a cada 6 meses ✔ 1 crise/3 meses ✔ concentração sérica >30ug/ml ✔ iniciar KBr – 30-40mg/kg/dia  BROMETO DE POTÁSSIO ✔ 30 a 40 mg/kg/SID ✔ ESTABILIZAÇÃO SÉRICA – 4 a 5 meses ✔ Dose de ataque: dose diária manut. + 80 mg/kg ✔ EFEITOS COLATERAIS  DIAZEPAN / MIDAZOLAN ✔Tratamento emergencial das crises ✔Intravenosa ✔Intraretal ✔Meia-vida curta ✔Efeito colateral  OUTROS FÁRMARCOS ANTICONVULSIVANTES ✔Felbamato ✔Gabapentina ✔Topiramato ✔...  STATUS EPILEPTICUS ✔ EMERGÊNCIA CLÍNICA! ✔ Convulsões > 5 min. ✔ Convulsões seguidas sem retorno da consciência entre elas  STATUS EPILEPTICUS EFEITOS ENCEFÁLICOS – Vasodilatação cerebral - Edema cerebral - ↑ PIC - Morte de neurônios  STATUS EPILEPTICUS EFEITOS SISTÊMICOS – Hipoglicemia – Arritmias cardíacas – Hipertensão sistêmica – Edema pulmonar – Taquicardia neurogênico – Hipertermia – CID – Acidose metabólica – Morte  STATUS EPILEPTICUS Parar as convulsões ✔ FLUIDOTERAPIA ✔ MIDAZOLAN / DIAZEPAN – cada 15 a 30 min  STATUS EPILEPTICUS Previnir convulsão nas próximas horas: ✔Diazepan em infusão contínua ✔Fenobarbital ✔Terapia VO  STATUS EPILEPTICUS CONVULSÕES REFRATÁRIAS: – Propofol – Anestesia inalatória - isoflurano – Pentobarbital  STATUS EPILEPTICUS ✔ MONITORAR: – Acesso IV, fluidoterapia – Vias aéreas e O2 – Equilíbrio ácido básico – Glicemia – Temperatura corporal - 38 a 39,5°C – Troca de decúbito cada 4 hs  FALHAS NA TERAPIA ✔ Falha em monitorar o nível sérico e/ou fazer os incrementos na dose oral ✔ Medicação e dosagem ✔ Tutor ✔ Tolerância farmacodinâmica ✔ Doença progressiva ✔ Cães de grande porte DÚVIDAS Received: 4 October 2023 Accepted: 19 October 2023 DOI: 10.1111/jvim.16928 CONSENSUS STATEMENT Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-to-date infor- mation on the pathophysiology, diagnosis, and treatment of clinically important animal diseases. The ACVIM Board of Regents oversees selection of relevant topics, identification of panel members with the expertise to draft the statements, and other aspects of assuring the integrity of the process. The statements are derived from evidence-based medicine whenever possible and the panel offers interpretive comments when such evidence is inadequate or contradictory. A draft is prepared by the panel, followed by solicitation of input by the ACVIM membership which may be incorporated into the statement. It is then submitted to the Journal of Veterinary Internal Medicine, where it is edited prior to publication. The authors are solely responsible for the content of the statements. ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats Marios Charalambous 1 | Karen Muñana 2 | Edward E. Patterson 3 | Simon R. Platt 4 | Holger A. Volk 1 1 University of Veterinary Medicine Hannover, Hannover, Germany Abstract 2 North Carolina State University, Raleigh, Background: Seizure emergencies (ie, status epilepticus [SE] and cluster seizures North Carolina, USA 3 [CS]), are common challenging disorders with complex pathophysiology, rapidly pro- University of Minnesota, Minneapolis, Minnesota, USA gressive drug-resistant and self-sustaining character, and high morbidity and mortal- 4 VetOracle, Diss, Norfolk, UK ity. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking. Correspondence Marios Charalambous, Bünteweg 9, D-30559 Objectives: To establish evidence-based guidelines and an agreement among board- Hannover, Germany. certified specialists for the appropriate management of SE and CS in dogs and cats. Email: [email protected] Animals: None. Materials and Methods: A panel of 5 specialists was formed to assess and summa- rize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recom- mendations, especially for the interventions where veterinary clinical evidence was lacking. Results: The majority of the evidence was on the first-line management (ie, benzodi- azepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a Abbreviations: AES, American Epilepsy Society; ASMs, antiseizure medications; BZDs, benzodiazepines; CNS, central nervous system; CS, cluster seizures; CSE, convulsive status epilepticus; CSF, cerebrospinal fluid; DZP, diazepam; EEG, electroencephalography; ILAE, International League Against Epilepsy; IM, intramuscular; IN, intranasal; IV, intravenous; IVETF, International Veterinary Epilepsy Task Force; LZP, lorazepam; MDZ, midazolam; NCSE, non-convulsive status epilepticus; R, rectal; SE, status epilepticus. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. J Vet Intern Med. 2024;38:19–40. wileyonlinelibrary.com/journal/jvim 19 20 CHARALAMBOUS ET AL. combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies. Conclusions and Clinical Relevance: Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; manage- ment of complications and underlying causes related to seizure emergencies should accompany antiseizure medications. KEYWORDS cat, dog, emergency seizure disorders, treatment 1 | I N T RO DU CT I O N required to cause permanent complications and neuronal injury.9,10,17,18,20 However, because the majority of seizures are brief, and once a seizure Seizure disorders, including status epilepticus (SE) and cluster seizures lasts >5 minutes, it is most likely to be prolonged and potentially non- (CS), are common neurological emergencies for veterinary clinicians in self-limiting,21 researchers and clinicians have broadly adopted and primary care, emergency, and specialty practice, and are associated accepted the 5-minute time frame as the defining element of SE. The aim with high morbidity and mortality. Status epilepticus, in particular, of this 5-minute cut-off time is to (i) minimize the risk of systemic and remains a therapeutic challenge in animals with a mortality rate of brain complications associated with continuous seizure activity reaching 25.3%-38.5%,1-3 and it can lead to irreversible brain damage and sys- up to 30 minutes, (ii) prevent worsening of the prognosis and drug resis- 4-8 temic complications, especially if treatment is delayed. Complica- tance associated with increasing duration of uncontrolled seizure activity, tions and molecular changes can occur early in the course of the and (iii) limit any potentially unfavorable outcomes and adverse effects disease.4-6,9,10 Seizures can rapidly become self-sustaining and refrac- associated with the prolonged administration of multiple therapeutic tory to standard antiseizure medications (ASMs).4-6,11 (including anesthetic) interventions for seizures that are brief and self- In veterinary medicine, several treatment schemes and algorithms limiting.17,18,22 have been proposed for the management of emergency seizure disor- Accordingly, ILAE has revised the definition of SE to include both ders. However, these recommendations are based mainly on individual of these vital time points and defines SE as any prolonged seizure last- expert opinions, lack official validation, and are characterized by con- ing >5 minutes.19 Specifically, “SE is a condition resulting either from siderable variation. Although official recommendations and consensus the failure of the mechanisms responsible for seizure termination or statements for the treatment of epilepsy have been published,12-16 from the initiation of mechanisms which lead to abnormally prolonged similar guidelines are lacking for the management of the emergency seizures (after time point T1 = 5 minutes); it is a condition that can seizure disorders. Therefore, the aim of this Consensus Statement is to have long-term consequences (after time point T2 = 30 minutes), unify current practices and establish evidence-based guidelines and including neuronal death and alteration of neuronal networks.” A simi- agreement among board-certified specialists, that can serve as recom- lar time frame of 5 minutes was used to define SE by the International mendations for the appropriate treatment of SE and CS in dogs Veterinary Epilepsy Task Force (IVETF); the task force also included ≥ and cats. 2 seizures without recovery of consciousness in between in their defi- nition of SE.23 This definition of SE provides guidance as to when emergency treatment should be initiated. Overall, T1 is the time point 2 | D E F I N I T I O N A N D C L A S SI F I C A T I O N by which treatment should have already been initiated; T2 represents the time at which neuronal damage or self-perpetuating alteration of 2.1 | Duration and frequency neuronal networks progresses, and hence, is the latest time by which SE should be under control.24 Seizures are considered an emergency when their duration is prolonged Status epilepticus may be divided into 4 stages that differ in terms and they are not self-limiting, or when they occur as a closely grouped of treatment options, sensitivity to the drugs used, and underlying series. Traditionally, seizures can be defined as “brief” or “prolonged” pathophysiological processes.4-6,25-27 Details are provided in Figure 1. 17,18 when their duration is 2 self-limiting seizures over a period of 24 hours. Cluster seizures, American Epilepsy Society (AES), SE has been referred to as continuous especially in high frequency, (i) can pose a risk similar to SE for seizure activity, or >1 sequential seizure without full recovery of con- seizure-related neuronal damage and complications, (ii) can progress sciousness in between, with a duration of >30 minutes.17,19 The time to SE, and (iii) are unlikely to cease or be appropriately controlled frame of 30 minutes was based on the duration of convulsive SE that is without rescue medication.30-32 CHARALAMBOUS ET AL. 21 (5-10 mins) (10-30 mins) (> 30 mins) (> 24 hours) Stage 1 Stage 2 Stage 3 Stage 4 Impending Established Refractory (Super)refractory Neurotransmier GABAAR decrease Excitatory & inhibitory Gene expression Pathophysiology release/imbalance Internalizaon of neuropepdes alteraons Ion channel GABAAR subunits release/imbalance opening/closing NMDAR & AMPAR +/- BBB drug upregulaon transporters upregulaon Treatment response First-line treatment First-line treatment First- & second-line First-, second- & third- Likely responsive Progressively less treatment line treatment responsive Likely minimally to non- Likely minimally to non- Second-line treatment responsive responsive Likely responsive Third-line treatment Likely responsive FIGURE 1 Illustration of the SE stages and their differences regarding underlying pathophysiological processes involved and sensitivity to the drugs used. 2.2 | Types and semiology means of seizure-related motor activity and the fact that EEG can be overloaded with movement and muscle artifacts makes EEG of limited According to ILAE, the clinical forms of SE in humans are differenti- clinical value. ated based on two taxonomic criteria: motor activity and impairment A similar classification can be applied to animals. However, the of consciousness. Therefore, SE can be characterized as (i) SE with broad clinical semiology of CSE and NCSE reported in humans has not prominent motor signs (ie, convulsive SE [CSE], myoclonic SE, focal been observed or officially described in animals. The most commonly motor SE, tonic SE, and hyperkinetic SE), or (ii) SE without prominent reported form of SE in animals is generalized (tonic-clonic) CSE.4,37-41 19,26,33,34 motor signs (ie, non-convulsive SE [NCSE]). Each type can be However, the diagnosis of CSE and, in particular, NCSE can be over- divided again according to the degree of impairment of consciousness. looked in veterinary patients mainly because of the broad lack of utili- Convulsive status epilepticus is characterized by impaired conscious- zation of and expertise in ictal EEG.42 There are only a few reports of ness with generalized or generalized with focal onset motor signs. the use of EEG for the diagnosis of NCSE.43,44 In the absence of EEG, Non-convulsive status epilepticus can be comatose or non-comatose. NCSE should be suspected in any animal with a prolonged period of Comatose NCSE usually is observed after CSE and is characterized by altered consciousness (comatose or non-comatose types) after suc- the absence of any motor activity, although subtle myoclonus or nys- cessful management of convulsive seizures, especially after the with- tagmus may be observed. Non-comatose NCSE usually occurs in the drawal of any general anesthetic or sedative drugs. Ideally, EEG form of generalized absence status (eg, human patients can be lethargic should be performed in any neurological veterinary patient with with altered behavior, have slow speech or abnormal movements impaired or absent consciousness to assess the possibility of NCSE including regional bilateral myoclonus of the eyelid, perioral or upper and before applying any specific treatment plan, but the panel limb area), or in the form of focal SE with impairment of consciousness acknowledges that doing so might not be practical in most veterinary (eg, human patients can be conversant and interactive but confused settings. and experiencing autonomic, sensory, visual, olfactory, gustatory, audi- tory or emotional symptoms).19,34-36 Overall, although apparent con- vulsions are absent in NCSE, subtle motor signs such as twitching, 3 | METHODOLOGY 19,34 blinking, extrapyramidal signs, or myoclonus may be observed. In addition, despite the absence of convulsive activity, NCSE still can lead This Consensus Statement is intended to produce guidelines for the to neuronal injury and apoptotic cellular mechanisms, making early rec- management of emergency seizure disorders in dogs and cats. A Con- ognition and treatment as important as in CSE.34 Ictal electroencepha- sensus Panel, consisting of 5 members, including 1 chairperson lography (EEG) is a valuable tool in the diagnosis of all types of SE but (MC) and 4 panelists (KM, NP, SP, HV), was formed with the aim to most importantly for NCSE, because the clinical signs are often subtle (i) perform a thorough assessment and systematic review of the litera- and nonspecific.19,35 In CSE, the combination of clinical diagnosis by ture, (ii) identify any gaps and share knowledge and clinical expertise, 22 CHARALAMBOUS ET AL. and (iii) introduce recommendations regarding the management of SE 3.2 | Screening and CS in dogs and cats. The recommendations of the panel were based on current relevant evidence and clinical experience. Experi- A 2-stage selection process was used. At stage 1, studies retrieved mental laboratory animal and basic research studies, as well as guide- from the search were included based on the title and abstracts. Only lines used in human medicine, also were reviewed to support the studies describing therapeutic outcomes regarding the management panel's statements, especially when veterinary clinical studies and of emergency seizures in companion animals were included. At stage experience were lacking. 2, the papers included from stage 1 were selected for full data extrac- After the establishment of the Consensus Panel, the chairperson tion according to the inclusion criteria and were assessed on the drafted the methodology which was approved by the panelists. After grounds of the quality of evidence and treatment outcomes. approval, all members (chairperson and panelists) proceeded sepa- rately through the steps of searching, screening, and assessing the evi- dence before drafting their recommendations. A modified Delphi 3.3 | Quality of evidence assessment process was used. Each panel member individually performed assess- ments of the evidence and drafted recommendations. The results The quality assessment method included modified criteria from previous from each panel member's assessments and recommendations were systematic reviews and meta-analysis.13-15 The elements of assessment gathered and anonymized by an independent ACVIM staff member included study design, study group sizes, and methods of evaluating and then were subjected to multiple rounds of review, through meet- treatment outcomes. A numeric scale was allocated to each element, ings that the panel convened. Remaining differences were resolved with higher scores indicating studies with a lower risk of bias. before a consensus was reached. Overall, the procedure included (i) a literature search, (ii) a screening of each study, (iii) an assessment of the quality of evidence and treat- 3.3.1 | Study design ment outcomes in each study, and (iv) drafting of recommendations. Blinded, randomized comparison group clinical trials (score 6). Open-labeled, randomized comparison group clinical trials (score 5). 3.1 | Literature search Open-labeled non-randomized clinical trials (score 4). Retrospective case series (score 3). Three scientific databases (MEDLINE/PubMed, Google Scholar and Case reports (score 2). CAB Abstracts) were used. Final electronic searches were carried out Expert opinions or personal views (score 1). during November 2022 by each member separately, with no date or language restrictions. The search terms used are provided in Supple- mentary file 1. Searching for articles from the reference lists of publica- 3.3.2 | Study group sizes tions and the proceedings of major veterinary neurology conference meetings (ie, the annual forum of the American College of Veterinary >30 subjects in total (score 3). Internal Medicine [ACVIM] and the symposium of the European Soci- 10-30 subjects in total (score 2). ety and College of Veterinary Neurology [ESVN/ECVN]) was also per- 50% of the members of score or 1 clinical study with an overall high-quality score evalu- study population in each treatment group were responders (ie, seizure ated the use of the intervention for the management of SE or CS termination). The 95% confidence interval (CI) was calculated using in dogs or cats. standard statistical methods with the aim to identify the true popula- III—“Low level of evidence for or against the intervention”: tion of responders. The interpretation of the 95% CI results for each when ≥1 clinical study with an overall low-quality score or 1 clinical study was as follows: study with an overall moderate quality score or when only pharmacokinetic studies exist, without any existing study with an 95% CI of the study's proportion of responders falling within a overall high-quality score, evaluated the use of the intervention for range of >50%: the intervention was considered as likely effective. the management of SE or CS in dogs or cats. 95% CI of the study's proportion of responders overlapping within IV—“Conflicting level of evidence”: when a minimum of 2 clinical a range between 50%: the intervention was considered studies (particularly with overall high-quality scores) evaluated the as possibly effective. use of a specific intervention for the management of SE or CS in 95% CI of the study's proportion of responders falling within dogs or cats as a primary treatment outcome; however, conflicting a range of 85 / MÉDIA > 60 mmHg AMBIENTE COM TEMP E UMIDADE CONTROLADOS ELEVAÇÃO DA CABEÇA COM TRAVESSEIROS MANTER PACIENTES SEDADOS EM DECÚBITO ESTERNAL  Terapêutica do sistema cardiovascular B-BLOQUEADOR SILDENAFIL TORACOCENTESE ABDOMINOCENTESE PERICARDIOCENTESE VALVULOPATIAS ADQUIRIDAS Profa Rebeca Bacchi  2  ENDOCARDIOSE  75 a 80 % das cardiopatias adquiridas em cães  Rara nos gatos  mitral - 62%;  mitral e tricúspide - 33%;  tricúspide - 1%  ENDOCARDIOSE  INCIDÊNCIA  Sexo - M:F = 1,5:1  Idade - meia idade a idosos > 5 anos  Raças de pequeno a médio porte < 20kg  1/3 pacientes > 10 anos  ENDOCARDIOSE  ETIOLOGIA  desconhecida  fator poligênico hereditário  FISIOPATOLOGIA Degeneração dos folhetos pequenos nódulos nas margens dos folhetos nódulos maiores nódulos coalescem folhetos enrijecidos, espessados e irregulares não coaptam na sístole regurgitação de sangue para AE lesões atriais ENDOCARDIOSE  IM aguda x crônica     ENDOCARDIOSE  SINAIS CLÍNICOS  tosse  síncope  dispneia  arritmia  cianose  sopro  Sasha, Poodle, F, 10 a Tosse alta, sopro sistólico mitral IV/VI   Sasha, Poodle, F, 10 a Tosse alta, sopro sistólico mitral IV/VI   Sasha, Poodle, F, 10 a Tosse alta, sopro sistólico mitral IV/VI   Budweiser, Poodle, M, 15 a Tosse, ascite, síncope Sopro holossistólico mitral (V/VI) e tricúpside (IV/VI)   Budweiser, Poodle, M, 15 a Tosse, ascite, síncope Sopro holossistólico mitral (V/VI) e tricúpside (IV/VI)   Budweiser, Poodle, M, 15 a Tosse, ascite, síncope Sopro holossistólico mitral (V/VI) e tricúpside (IV/VI)   Budweiser, Poodle, M, 15 a Tosse, ascite, síncope Sopro holossistólico mitral (V/VI) e tricúpside (IV/VI)   Budweiser, Poodle, M, 15 a Tosse, ascite, síncope Sopro holossistólico mitral (V/VI) e tricúpside (IV/VI)   Kiko, SRD, M, 12 a Emagrecimento, tosse, dispnéia Sopro holossistólico mitral (IV/VI), taquicardia, crepitações pulmonares   Kiko, SRD, M, 12 a Emagrecimento, tosse, dispnéia Sopro holossistólico mitral (IV/VI), taquicardia, crepitações pulmonares   Kiko, SRD, M, 12 a Emagrecimento, tosse, dispnéia Sopro holossistólico mitral (IV/VI), taquicardia, crepitações pulmonares   ENDOCARDIOSE  EXAMES COMPLEMENTARES - Eletrocardiograma  inespecífico  normal  aumento AE e VE  taquicardia sinusal  arritmias  ENDOCARDIOSE  EXAMES COMPLEMENTARES - Radiografia  Aumento de AE e VE  ICC (congestão e edema pulmonar)  Compressão de brônquio principal esquerdo  ENDOCARDIOSE  EXAMES COMPLEMENTARES - Ecocardiograma  Aumento de AE / AD  espessamento dos folhetos valvares  VE hiperdinâmico  Ruptura de cordoalha tendínea  DOPPLER: detecta e quantifica a insuficiência  ENDOCARDIOSE  DIAGNÓSTICO DIFERENCIAL  SOPRO  TOSSE  IM secundária  traqueobronquite infecciosa  endocardite bacteriana  colapso de traquéia  cardiopatias congênitas  brônquite crônica  anemia  ENDOCARDIOSE  CLASSIFICAÇÃO  A – cães predisponentes  B1 – sopro sem aumento cardíaco  B2 – sopro com aumento cardíaco  C – sinais atuais ou anteriores de ICC  D – ICC refratária  ENDOCARDIOSE  TRATAMENTO  A– cães predisponentes  Avaliações regulares  B1 – Avaliações regulares  B2 – pimobendan* / IECA / dieta hipossodica  C – Edema pulmonar (hospital) + tto domiciliar  D - ….  ENDOCARDIOSE  PROGNÓSTICO  compensados - bom  sinais ICC - reservado  Cavalier King Charles Spaniel CARDIOMIOPATIAS CANINAS Rebeca Bacchi   CARDIOMIOPATIAS CANINAS SECUNDÁRIAS PRIMÁRIAS CM dilatada ***  Doxorrubicina  CM hipertrófica  Hipertireoidismo  HAS  Neoplasia  CARDIOMIOPATIA DILATADA ◼ Miocardiopatia primária ◼ Caracterizada por disfunção sistólica Dilatação das câmaras ventriculares e atriais cardíacas de forma unilateral ou bilateral 4   CARDIOMIOPATIA DILATADA  INCIDÊNCIA  Sexo – M > F  Idade – 4 a 8 anos  Raças GRANDE PORTE / GIGANTE  CARDIOMIOPATIA DILATADA  ETIOLOGIA  Idiopática  Familiar ou genética  Nutricional  Deficiência de taurina (cocker, golden)  Deficiência de L-carnitina (cocker, boxer)  CONTRATILIDADE ARRITMIAS  DC e  PA fraqueza, síncope, choque cardiogênico Ativação de mecanismos Sinais de ICC compensatórios (congestão/edema/efus ão) 8   CARDIOMIOPATIA DILATADA  SINAIS CLÍNICOS  intolerância ao  Ascite/hepatomegalia exercício  edema de membros  tosse  pulso fraco  dispnéia  pulso jugular  síncope  perda de peso/caquexia  fraqueza cardíaca 11  CARDIOMIOPATIA DILATADA  SINAIS CLÍNICOS – auscultação  ritmo de galope (S3)  sopro sistólico I a III/VI  arritmia  crepitações pulmonares  CARDIOMIOPATIA DILATADA  EXAMES COMPLEMENTARES  Radiografia torácica  Eletrocardiograma / holter  Ecocardiograma RADIOGRAFIA TORÁCICA RADIOGRAFIA TORÁCICA RADIOGRAFIA TORÁCICA ELETROCARDIOGRAMA Fibrilação atrial ELETROCARDIOGRAMA Taquicarda sinusal com VPC ELETROCARDIOGRAMA Complexo ventricular prematuro Taquicarda ventricular sustentada ELETROCARDIOGRAMA Taquicarda ventricular sustentada  ECOCARDIOGRAMA  Dilatação atrial e ventricular  Hipocinesia de VE  Redução da função sistólica do miocárdio  Regurgitação mitral / tricúspide ECOCARDIOGRAMA ECOCARDIOGRAMA ECOCARDIOGRAMA ECOCARDIOGRAMA  Shatzi, Cocker, F, 9a Cansaço, tosse, dispnéia, emagrecimento  Sopro sistólico Mitral, grau II/VI, ritmo irregular, pulso fraco ECOCARDIOGRAMA ECOCARDIOGRAMA  Amigo II, doberman, M, 4 anos Emagrecimento, cansaço, dispnéia, tosse  Ritmo irregular, sopro sistólico mitral, grau II/VI, pulso fraco RADIOGRAFIA TORÁCICA     CARDIOMIOPATIA DILATADA  TRATAMENTO SEM ICC  Educar o cliente  Digoxina  Inibidor da ECA  Taurina 500 mg/BID ou TID/VO (cocker, golden)  L-carnitina 50-100 mg/kg/TID/VO (cocker, boxer)  CARDIOMIOPATIA DILATADA  TRATAMENTO COM ICC  4 D’s  Taurina 500 mg/BID ou TID/VO (cocker, golden)  L-carnitina 50-100 mg/kg/TID/VO (cocker, boxer)  Pimobendan (inotrópico + vasodilatador)?!?!?!  CARDIOMIOPATIA DILATADA  TRATAMENTO ARRITMIAS VENTRICULARES  CARDIOMIOPATIA DILATADA  TRATAMENTO ARRITMIAS VENTRICULARES  Mexiletine 4-8 mg/kg/TID/VO  Sotalol 0,5-2mg/kg/BID/VO  Amiodarona 10-20mg/kg/SID/VO 7 a 10 dias, após 3- 15mg/kg/SID/VO  Lidocaína / procainamida (VPCs sustentadas)  CARDIOMIOPATIA DILATADA  TRATAMENTO FIBRILAÇÃO ATRIAL  Digoxina  Diltiazen 0,5-2,5 mg/kg/TID/VO  Propranolol 0,2-1 mg/kg/TID/VO  Atenolol 6,25-12,5 mg/cão BID ou SID/VO  CARDIOMIOPATIA EM BOXER  Cardiomiopatia arritmogênica ventricular direita  Hereditária  Apoptose de cardiomiócitos infiltrado de tecido fibroso e gordurosono VD  CARDIOMIOPATIA EM BOXER  1) ASSINTOMÁTICOS  Ausência de sinais clínicos  Arritmias ventriculares  Pode ocorrer morte súbita  CARDIOMIOPATIA EM BOXER  2) SÍNCOPES  CVPs (VD)  Pode evoluir para ICC  Pode ocorrer morte súbita  CARDIOMIOPATIA EM BOXER  3) ICC  Miocardiopatia dilatada  Prognóstico ruim  CARDIOMIOPATIA EM BOXER  SINAIS CLÍNICOS  Ausente  Arritmia  Sopro/ritmo de galope (S3)  Sinais de ICC CARDIOMIOPATIA EM BOXER Taquicardia ventricular CARDIOMIOPATIA EM BOXER Taquicardia ventricular  CARDIOMIOPATIA EM BOXER  EXAMES COMPLEMENTARES  Radiografia torácica  Eletrocardiograma / HOLTER  Ecocardiograma  CARDIOMIOPATIA EM BOXER  TRATAMENTO  Arritmias ventriculares  ICC quando presente  Suplementação nutricional CARDIOMIOPATIAS FELINAS  CARDIOMIOPATIAS FELINAS CM hipertrófica ***  CM restritiva  CM dilatada  CM arritmogênica VD  CARDIOMIOPATIA HIPERTRÓFICA PRIMÁRIA*** = IDIOPÁTICA (familiar)  SECUNDÁRIA  CARDIOMIOPATIA HIPERTRÓFICA  Disfunção diastólica do miocárdio  Origem hereditária: maine coon, americano de pelo curto e persa  Machos (87%)  Adultos (4 a 7 anos)  FISIOPATOLOGIA  HIPERTROFIA espessura parede cavidade VE DC  FISIOPATOLOGIA  HIPERTROFIA rigidez miocárdica disfunção diastólica pressão diastólica e pressão AE AE estase sanguínea trombo regurgitação mitral pressão venosa pulmonar=edema pulmonar 54  CARDIOMIOPATIA HIPERTRÓFICA  SINAIS CLÍNICOS  Assintomáticos  Paralisia / paresia dos MPs  Pulso normal, fraco ou ausente  Leito ungueal cianótico  Dor  dispnéia / posição ortopneica  ICC  CARDIOMIOPATIA HIPERTRÓFICA  SINAIS CLÍNICOS – auscultação  ritmo de galope – S3 (40%)  sopro sistólico (60%)  Arritmia (25%)  crepitações pulmonares  abafamento de sons  CARDIOMIOPATIA HIPERTRÓFICA  EXAMES COMPLEMENTARES  Radiografia torácica  Eletrocardiograma  Ecocardiograma RADIOGRAFIA TORÁCICA RADIOGRAFIA TORÁCICA RADIOGRAFIA TORÁCICA ECOCARDIOGRAMA ECOCARDIOGRAMA ECOCARDIOGRAMA  CARDIOMIOPATIA HIPERTRÓFICA  DIAGNÓSTICOS DIFERENCIAIS  Hipertireoidismo  HAS  Estenose sub-aórtica  CARDIOMIOPATIA HIPERTRÓFICA  TRATAMENTO EMERGENCIAL  DIURÉTICO  VASODILATADOR  OXIGÊNIO  TORACOCENTESE  REPOUSO  CARDIOMIOPATIA HIPERTRÓFICA  TRATAMENTO DOMICILIAR  DIURÉTICO  ß-BLOQUEADOR  PROPANOLOL / ATENOLOL  BLOQUEADOR DE CANAL DE CÁLCIO  DILTIAZEM / VERAPAMIL  INIBIDORES DA ECA  BENAZEPRIL / ENALAPRIL  FORMAÇÃO DE TROMBOS NO AE TROMBO SE DESPRENDE AORTA FINAL AORTA BRAQUIAL A. ILÍACAS A. RENAL A. MESENTÉRICA 74  CARDIOMIOPATIA HIPERTRÓFICA  TRATAMENTO TROMBOEMBOLISMO  PREVENTIVO  Terapia anticogulante (heparina e warfarin)  Terapia antiplaquetária (aspirina)  CURATIVO  Terapia trombolítica (estreptoquinase)  Cirurgia !?!?!  APOIO  CARDIOMIOPATIA HIPERTRÓFICA  PROGNÓSTICO Received: 6 March 2019 Accepted: 13 March 2019 DOI: 10.1111/jvim.15488 CONSENSUS STATEMENT Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-to-date information on the pathophysiology, diagnosis, and treatment of clinically important animal diseases. The ACVIM Board of Regents oversees selection of relevant topics, identification of panel members with the expertise to draft the statements, and other aspects of assuring the integrity of the process. The statements are derived from evidence-based medicine whenever possible and the panel offers interpretive comments when such evidence is inadequate or contradictory. A draft is prepared by the panel, followed by solicitation of input by the ACVIM membership which may be incorporated into the statement. It is then submit- ted to the Journal of Veterinary Internal Medicine, where it is edited prior to publication. The authors are solely responsible for the content of the statements. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs Bruce W. Keene1 | Clarke E. Atkins1 | John D. Bonagura1,2 | Philip R. Fox3 | 4 5 6 7 Jens Häggström | Virginia Luis Fuentes | Mark A. Oyama | John E. Rush | 8 9 Rebecca Stepien | Masami Uechi 1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State Abstract University, Raleigh, North Carolina This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises 2 Department of Veterinary Clinical Sciences, guidelines for the diagnosis and treatment of myxomatous mitral valve disease The Ohio State University, Columbus, Ohio 3 The Elmer and Mamdouha Bobst Hospital, The (MMVD, also known as endocardiosis and degenerative or chronic valvular heart dis- Animal Medical Center, New York, New York ease) in dogs, originally published in 2009. Updates were made to diagnostic, as well 4 Department of Clinical Sciences, Swedish University as medical, surgical, and dietary treatment recommendations. The strength of these of Agricultural Sciences, Uppsala, Sweden 5 Department of Clinical Science and Services, recommendations was based on both the quantity and quality of available evidence Royal Veterinary College, London, United Kingdom supporting diagnostic and therapeutic decisions. Management of MMVD before the 6 Department of Clinical Sciences and onset of clinical signs of heart failure has changed substantially compared with the Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and 7 Department of Clinical Sciences, Cummings pulmonary hypertension are reviewed. School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts KEYWORDS 8 Department of Medical Sciences, University canine, congestive heart failure, evidence-based treatment, mitral of Wisconsin, Madison, Wisconsin 9 Jasmine Veterinary Cardiovascular Medical Center, Yokohama, Japan Correspondence Bruce W. Keene, College of Veterinary Medicine, North Carolina State University, 1052 William Moore Drive, Raleigh, NC 27607. Email: [email protected] Abbreviations: ACEI, angiotensin converting enzyme inhibitors; Ao, aorta; BW, body weight; CHF, congestive heart failure; CRI, constant rate infusion; IM, intramuscularly; LA, left atrium; LOE, level of evidence; LV, left ventricle; LVIDD, left ventricular end diastolic diameter; LVIDd, left ventricular end diastolic diameter in diastole; LVIDdN, left ventricular end diastolic diameter normalized for body weight; MMVD, myxomatous mitral valve disease; MR, mitral regurgitation; NT-proBNP, N-terminal pro-B-type natriuretic peptide; VHS, vertebral heart score; VLAS, vertebral left atrial size. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. J Vet Intern Med. 2019;33:1127–1140. wileyonlinelibrary.com/journal/jvim 1127 1128 KEENE ET AL. 1 | I N T RO D UC T I O N use a hybrid of the American Heart Association and Veterinary Emergency Critical Care RECOVER evidence grading criteria, as out- The panel adopted the following scheme, adapted from the American lined below.1,2 Heart Association,1 to rate the strength of the recommendations in these guidelines. The recommendation class designation appears with each rec- 3.1 | Strong ommendation, along with a second term that independently rates the quality of the evidence upon which the recommendation was based. High-quality evidence is from ≥1 randomized controlled trial, or a moderate-quality randomized controlled trial, corroborated by a high- quality observational study or other moderate-quality trials. These 2 | CLASS I FICAT I ON OF prospective clinical studies were performed in dogs and either ran- RECOMMENDATIONS domly allocated subjects to an intervention or control group or used concurrent controls (ie, controls recruited at the same time as the Class I recommendations are strong, reflecting the panel's conviction experimental subjects) without randomization. Strong evidence also that the recommended action appears to have definite benefit for could have been obtained from prospectively enrolled, controlled, most patients, outweighing the risk to most patients. observational clinical studies in dogs with spontaneously occurring Class I recommendations can be summarized as “benefit >>> risk”. mitral valve disease. These studies asked clinically relevant questions, Class IIa recommendations are moderately strong, reflecting the were considered to be adequately powered, and did not experience panel's belief that the recommended action should benefit most excessive loss of subjects to follow up in any group, generating a clear patients, probably outweighing the risk to most patients. and statistically valid result. Class IIa recommendations can be summarized as “benefit >> risk”. Class IIb recommendations are weak, reflecting the belief that the recommended action possibly benefits some patients and may out- 3.2 | Moderate weigh the risk of taking the proposed action in most patients. Moderate-quality evidence is from ≥1 well-designed, well-executed Class IIb recommendations can be summarized as “benefit > risk”. nonrandomized studies, observational studies, or registry studies, or Class III is used to describe recommendations in which the panel meta-analyses of such studies. Evidence rated as “moderate” by the believes that the potential risk and benefit of the proposed action are panel was generated from controlled, retrospective studies in dogs essentially equal, such that these actions should probably not be pur- (ie, studies in which dogs with mitral valve disease [or appropriate sued under most circumstances. controls] were selected from a previous period in time). Moderate Class III recommendations can be summarized as “benefit = risk”. evidence also could have been generated from blinded and con- Class IV recommendations indicate the panel's belief that the pro- trolled laboratory studies that were performed in experimental dogs. posed action is more likely to cause harm than benefit to most patients, such that Class IV designates actions that the panel believes are contraindicated under most circumstances. 3.3 | Weak Class IV recommendations can be summarized as “risk >> benefit”. Weak-quality evidence is from randomized or nonrandomized obser- The recommendation classification and level of evidence (LOE) vational or registry studies with limitations of design or execution, upon which that recommendation was based were independently but performed in dogs with clinical myxomatous mitral valve disease determined by the panel (ie, any class of recommendation may be (MMVD), or physiological, mechanistic, or experimental studies per- paired with any LOE). formed in research dogs. Evidence rated as “weak” by the panel was The panel acknowledges that future evidence may change the generated from uncontrolled clinical case reports or case series in strength of any of these recommendations, as well as the quality of the dogs with mitral valve disease, as well as by experimental or clinical evidence on which they are based. Many important clinical questions studies that were not performed in dogs with MMVD. These could addressed in the guidelines have not yet been adequately addressed by include experimental models of mitral valve disease in other species, clinical trials. At times, the panel has made strong recommendations as well as high-quality studies in humans (such as meta-analyses, ran- based on more than the available evidence—thus weak or even absent domized controlled trials, and clinical studies with concurrent con- evidence does not necessarily accompany a weak recommendation. trols, including observational studies) with spontaneous mitral valve Although randomized clinical trial evidence may be unavailable, a clear disease. clinical consensus that a particular test or treatment is useful may exist. 3.4 | Expert opinion 3 | L EV E L S O F E V I D E N C E Expert opinion based on clinical experience, common sense, or physi- The methods of assessing the quality of the scientific evidence that ologic or mechanistic studies performed in species other than dogs is supports clinical decision making are evolving. The panel chose to considered the weakest LOE. KEENE ET AL. 1129 4 | INCIDENCE, PATHOLOGY, AND It has been hypothesized that abnormal numbers or types of mito- PATHOGENESIS OF MMVD gen receptors (ie, any of the subtypes of serotonin, endothelin, or angio- tensin receptors) on fibroblast cell membranes in the valves of affected It is estimated that approximately 10% of dogs presented to primary dogs play a role in the pathophysiology of acquired valvular lesions.21–23 care veterinary practices have heart disease, and MMVD is the most Systemic or local metabolic, neurohormonal, or inflammatory mediators common heart disease of dogs in many parts of the world, accounting (eg, endogenous catecholamines, inflammatory cytokines) also may for approximately 75% of heart disease cases seen in dogs by veteri- influence progression of the valve lesion or the subsequent myocardial nary practices in North America. remodeling and ventricular dysfunction that accompany long-standing, The pathology of MMVD has been relatively recently reviewed,3 hemodynamically important valvular regurgitation. The interactions of and some progress in understanding the genetics and pathophysiology these factors, as well as the impact of changes in mitral valve annular 4,5 geometry and mechanical stress on the pathogenesis and progression of the disease has been reported. Myxomatous mitral valve disease most commonly affects the left atrioventricular or mitral valve, although of MMVD, are incompletely understood.11–13,24 in at least 30% of cases, the right atrioventricular (tricuspid) valve also is The prevalence of MMVD increases markedly with age in small 6 involved. The disease is approximately 1.5 times more common in breed dogs, with up to 85% showing evidence of the valve lesion by males than in females. Prevalence is also higher in smaller (