1 Michele Borgarelli

Transcription

1 # Michele Borgarelli 1 1 DVM, PhD, DipECVIM-CA (Cardiology) Associate Professor Virginia- Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA

2 MAKING TOMORROW HAPPEN TODAY Is a dog with Stage B2 Chronic Degenerative Mitral Valve Disease always pre-clinical? M. Borgarelli Blacksburg, VA, USA

3 DISCLOSURE Grants/Research contracts: Ceva Santé Animale Consulting: Ceva Santé Animale

4 10 yrs, FS, Min Schnautzer No clinical signs have been noticed by the owner Grade IV/VI left apical murmur HR 140 bpm LUNA

5 LUNA

6 LUNA CHRONIC DEGENERATIVE MITRAL VALVE DISEASE (MMVD) STAGE ACVIM B2

7 1 week later she developed acute onset of dyspnea Diffuse interstitial-alveolar pattern on radiographs No rupture of major chordae was identified LUNA

8 LUNA: questions Was Luna in heart failure at the time of first presentation? How can we improve the diagnosis of heart failure? Should we revise guidelines for the diagnosis and management of heart failure in dogs with MMVD?

9 Preclinical MMVD definition J. Vet. Int. Med STAGE B Patients with structural heart disease, but that have never developed clinical signs caused by heart failure STAGE B1 No radiographic or echocardiographic evidence of cardiac remodeling STAGE B2 Significant MR as evidenced by radiographs or echo

10 Preclinical MMVD definition B Current definition of preclinical disease (STAGE B) identifies a heterogeneous group of patients affected by mild, moderate and severe disease 2

11 MMVD PATHOPHYSIOLOGY WHEN NEUROHORMONAL RESPONSE IS ACTIVATED IN DOGS WITH MMVD? Orton C et al. JVC, 2012

12 PATHOPHYSIOLOGY DECREASED CARDIAC OUTPUT ECHOCARDIOGRAPHIC CHANGES MAY REFLECT THE CARDIAC SEVERITY REMODELING OF THE DISEASE AND LIKELY THE LEVEL OF NEUROHORMONAL ACTIVATION ACTIVATION OF COMPENSATORY MECHANISMS (SNS, RAAS, ADH,NATRIURETIC PEPTIDES) Pulmonary edema

13 . Echocardiographic is the principal investigation and must include an assessment of severity, mechanism, reparability and consequences

14 J. Vet. Int. Med In small breed dogs echocardiographic is recommended to answer specific questions regarding either cardiac enlargement or the cause of the murmur

15 Survival characteristics Mean survival time days Log Rank P =

16 WHEN DO DOGS WITH MMVD DEVELOP HEART FAILURE? The natural history of MMVD is long and understanding the life history requires long-term follow up with serial evaluation, i.e. both the physician and the patient must live for a long time. Boudoulas KD

17 DIAGNOSIS OF HEART FAILURE HF is a complex syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood The cardinal manifestation of HF are dyspnea and exercise intolerance Because some patients present without signs or symptoms of volume overload the term Heart Failure is preferred over Congestive Heart Failure

18 Preclinical MMVD definition J. Vet. Int. Med STAGE C Patients with structural abnormality and current or previous clinical signs of heart failure caused by MMVD What clinical signs?

19 DIAGNOSIS OF HEART FAILURE J. Vet. Int. Med In veterinary medicine is generally accepted that diagnosis of heart failure is based on evidence of pulmonary edema on thoracic radiographs Current guidelines recommend to obtain thoracic radiographs to determine the cause of clinical signs This is the definition of Congestive Heart Failure The current guidelines do not mention what are the clinical signs that should be considered suggestive of heart failure

20 Clinical signs of heart failure Dyspnea/tachypnea? At rest? Exercise intolerance How to assess it Weight loss How much can we rely on owner ability to recognize the presence of clinical signs?

21 Clinical signs of heart failure RESPIRATORY RATE Correlate with total lung water content In dogs normal RR at rest < 30 RR at the time of presentation to the hospital predicts congestive heart failure in dogs with MMVD and DCM Resolution of CHF is associated with a decrease of RR in dogs with MMVD and DCM MMVD DCM Wang et al. Pacing Clin Electrophysiol 2005 Schober et al. J Vet Int Med, 2010 Schober et al J Am Vet Med Assoc 2011 Rishniw et al Res in Vet Sci, 2012

22 Clinical signs of heart failure COUGH Cough is not associated with the presence of heart failure in dogs with MMVD Cough is associated with abnormal radiographic airway pattern LA enlargement is associated with an increased risk for cough

23 PULMONARY HYPERTENSION 24/100 (29%) ACVIM B2 dogs had pulmonary hypertension due to left-sided heart disease PH defined by a TR > 3 m/sec

24 LUNA Left atrium Significant cardiac remodeling No clinical signs accordingly to the owner No convincing evidence of pulmonary edema on radiographs Several echocardiographic predictors of poor outcomes LA enlargement E wave peak velocity > 1.2 OR 3.3 p< E wave > 1.2 m/sec < 1.7 > 1.7 < 1.2 m/sec OR 2.3 p< 0.001

25 Biomarkers Hezzell M.J., et al J Vet Intern Med Low: hsctni < ng/ml NT-proNP < 524 pmol/l Medium: hsctni < ng/ml NT-proNP > 524 pmol/l hsctni > ng/ml NT-proNP < 524 pmol/l High: hsctni > ng/ml NT-proNP > 524 pmol/l CONCLUSION AND CLINICAL IMPORTANCE: Serum hsctni has progrostic value in dogs with MMVD. Measurement of NT-proBNP and hsctni is prognostically superior to measuring either alone. Serial measurement strategies provide additional progrostic information.

26 Stage B2 What s going on?

27 Preclinical MMVD: on going studies The EPIC STUDY Effect of Pimobendan on onset of Heart Failure in dogs with advanced preclinical MMVD Double blind multicenter study 36 centers all over the world 360 dogs Study period

28 Preclinical MMVD: on going studies THE EPIC STUDY Primary Objectives To evaluate the Efficacy of pimobendan therapy on delaying time of onset of clinical signs in dogs with advanced preclinical MMVD The study was terminated earlier because overall evidence of pimobendan benefit over placebo

29 Preclinical MMVD: on going studies DELay of Appearance of symptoms of canine degenerative mitral valve disease treated with Spironolactone and Benazepril Single blind multicenter study Most of the owner blinded 25 centers in Italy, UK and Netherland 240 dogs Study period

30 Preclinical MMVD: on going studies Primary Objectives To evaluate the Efficacy of spironolactone in combination with benazepril therapy on delaying time of onset of clinical signs in dogs with advanced preclinical CDVD To evaluate if NT-proBNP and high sensitivity Troponin I are useful prognostic indicators for time of onset of clinical signs in the same population of dogs This study is currently ongoing (results of interim analysis pending)

31 Preclinical MMVD: on going studies The EPIC and the DELAY Study Design end point: first onset of CHF AND Onset of clinical signs

32 The EPIC and DELAY Advanced preclinical disease Severe LA enlargement LV enlargement More homogeneous group of patients compare to previous studies High risk of progression Absence of clinical signs reported by the owners It is possible that some of these dogs were in heart failure at the time of inclusion

33 Preclinical MMVD: conclusions Stage B2 MMVD includes a heterogeneous group of dogs Need further studies to identify risk factors able to recognize dogs with higher risk of progression Multifactorial? Biomarkers? Is echocardiography a better way to assess the severity? Need to revise current guidelines for management of the disease * VETPROOF: MR Severity Index Difference: Time to CHF <150 vs = 1yr <150 vs > yr vs >250=1.2yr (Age/10) X (HR/120) LA:AO * Difference: Entry to Death <150 vs = 1.8yr <150 vs >250=2.7 yr vs >250=.9yr Atkins, et al. Proc. ACVIM

34 To change opinion and follow who corrects you Is the essence of the free man Marco Aurelio THANK YOU FOR YOUR ATTENTION

35 # 1 Is a dog with Stage B2 Chronic Degenerative Mitral Valve Disease always pre-clinical? 35 Stage B2 MMVD includes a heterogeneous group of dogs Need further studies to identify risk factors able to recognize dogs with higher risk of progression Is echocardiography a better way to assess the severity? Need to revise current guidelines for management of the disease