Cardiology - Myxomatous Mitral Valve Degeneration: What's New? By Rita Singh

1. Dr Rita Singh
BSc, BVMS, DipVetClinStud, FANZCVS, Dip
ACVIM (Cardiology)

2.  Most common heart disease of dogs
 Toy poodle, Maltese, ShihTzu, Dachshund,
Miniature Schnauzer, Chihuahua,Yorkshire
Terrier,Whippet,
 CKCS: 50% affected by 7 years
 Large breeds: GSD, Doberman, ACD,
Dalmation, X’s

3.  Mitral valve apparatus:
 Valve leaflets
 Annulus
 Chordae tendinae
 Papillary muscles

4.  Mucopolysaccarides
 Appearance of embryonic mesenchymal tissue
 Collagen degeneration
 Endothelial
proliferation

5. • Pathology alters valve
motion:
• Valve thickening
• Prolapse
• Annular dilation
• Mitral regurgitation

7. Murmur Grading
 Soft murmur (grades I-III) = mild disease
 Loud murmur (grade IV-VI) = mild,
moderate or severe disease

8.  Grading of murmurs:
 I:Very soft. Only heard in a quiet room with
concentration
 II: Faint but easily heard
 III: Moderately loud but localized to a single
area
 IV: Loud and radiates over the chest
 V: Loud. Palpable thrill
 VI:Thrill. Heard with stethoscope just off chest

9.  Location is important to differentiate cause
 Mitral murmur: best heard at the left apex:
where you can palpate the apex beat
 Left basilar murmur: SAS, PS, hyperdynamic
state

10.  Slow disease progression
 558 dogs followed over ~ 3 yrs
 60% alive or died of non cardiac related
causes
 Can be benign
 CKCS?
 Kvart et al JVIM
2002
 Mean time to CHF
27 months

11.  Baroreceptors detect
reduced CO
 Stimulate SNS
 HR and contractility
 Arteriolar constriction
 Normalizes
haemodynamics

12.  β1 receptors down-
regulate
 CHF – approx 50%
can’t stimulate
 Improved rate and
contractility
diminishes
 What now??

13.  BP
 β1 stimulation
 Renal perfusion
 Na+ resorption
Stimulates renal release of renin

14. Renin – Angiotensin –
Aldosterone System
Sympathetic
efferent activity
Diuretics
Na to
distal
tubule
Renal
perfusion
K+, Ca++
PGl
ANP
Renin
release
Angiotensinogen
(liver)
Angiotensin I
(lung)
Angiotensin II
ACE
Thirst
Vasoconstriction
Na retention
Aldosterone
secretion
(adrenal)
ADH secretion
(pituitary)

15.  Progression forward SV
 LA pressure
 Pulmonary capillary pressure
 Pulmonary oedema
 Medication is essential

16.  CHF results from SEVERE heart disease
 Treatment NOT required with mild
disease
 Exception: acute chordal rupture

18.  Once in heart failure:
 Average survival 12 months
 Large breed dogs: ~ 6 months?
 Take Home Message!!
 Reconsider diagnosis if your CHF
patient is running around and
happy 4 yrs later

20.  Penny
 9y FS CKCS X Maltese, 8 kg
 Presenting complaint: Coughing
 1-2x/day for 2 years
 8-10x/day for 6 months
 Current treatment:
 Frusemide 20 mg q 12 hrs
 Pimobendan 2.5 mg q 12 hrs
 Benazepril 2.5 mg q 24 hrs
 Spironolactone 25 mg q 12 hrs

21.  T: 37.9
 HR 100 bpm
 PR 100 bpm
 Resp sinus arrhythmia
 RR 24, eupneac
 MM pink, CRT 1 sec, tacky
 Grade IV/VI left apical systolic murmur

22.  Signalment and murmur consistent with
MMVD
 IV/VI murmur could be consistent with CHF
 HR, sinus arrhythmia, and RR are not
consistent with CHF
 Long history of cough suggests chronic
airway disease
 Plan: Chest xrays, Echocardiogram, Blood
Work

25.  Stopped cardiac medications
 Doxycycline 5 mg/kg bid 3 weeks
 Theophylline 10 mg/kg bid 3 weeks
 Bronchoscopy

26. 1. 100% collapse left cranial lobar
bronchus
2. 100% collapse left caudal
lobar bronchus
3. 100% collapse right middle lobar
bronchus

27.  Staging disease
 Assessing severity
 Assessing cause cough
 Assessing possibility and severity
of CHF

29.  MMVD:
 Diagnosis?
 Severity
 Chordal rupture
 Pulmonary hypertension
 Left atrial tear
 NOW ALMOST ESSENTIAL for staging
of the disease (EPIC)

30.  NYHA, ISACHC
 ACVIM Consensus Statement*
 A: High risk of developing MMVD but don’t currently
have the disorder
 B1: Has structural disease, asymptomatic, no cardiac
remodelling
 B2: Asymptomatic but has left heart enlargement
 C: Has had congestive heart failure (past or current)
 D: End stage disease. Refractory to standard therapy
* Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease, Atkins et al, JVIM 2009

31.  Stage A: Preclinical stage
 Dogs such as the CKCS and other small breed
dogs
 At high risk of developing MMVD
 Don’t yet have clinical evidence of the
disorder
 No treatment

32.  Stage B1: Has
structural disease
 Heart murmur
 No clinical signs
 No evidence of
cardiomegaly (echo
or rads)
 No treatment

33.  Stage B2: Typical murmur
of MMVD
 Asymptomatic
 BUT has evidence of
cardiomegaly –
radiographicAND
echocardiographic
 Treatment is now indicated
 Pimobendan 0.25 mg/kg bid

36.  Stage C is the patient
with clinical signs of
CHF (past or current)
associated with severe
MMVD
 Long term treatment is
ALWAYS indicated

38.  Older than 7 yrs and < 15 kg
 Loud murmur (IV/VI or >)
 Sinus arrhythmia absent
 Tachycardic (HR >120 bpm)
 Dyspneac (sleeping RR > 30)
**Cough on its own is not considered a
sign of congestive heart failure**
* Beijerink, Campbell, Gavaghan, Singh and Wooley. Published online via Vetforum, Boehringer Ingelheim, 2015

39.  O2 and frusemide before echo!
 Body weight – need to lose 7-10% BW
 Renal panel, urinalysis prior if possible

40.  Tachypnea (RR 40-60)
 Dyspnea +/- cough
 Tachycardic (>120 bpm)
 Loud mitral murmur (>IV/VI)
 Cardiomegaly and pulmonary
oedema
 Frusemide, ACEI, Pimobendan

41.  Loop diuretic
 Effective
 Many routes/doses
 Mild –mod HF: 1-3
mg/kg q 8-12 hr
 Severe/refractory: 4
mg/kg q 8 hr
 Very few side affects

42.  Blocks conversion of AgI AgII
 Decreases plasma aldosterone
 Mild arteriolar/venous dilation
 Less Na+/H2O retention
 Reduces pathologic remodelling/ fibrosis
 No evidence for use prior to CHF
 Benazepril 0.25-0.5mg/kg
sid
Angiotensin I
(lung)
Angiotensin II
ACE

43.  Increases binding affinity of
calcium to cTNc
 Inhibits cardiac PDE III →
reduces breakdown of cAMP →
increase ß stim
 Improves myocardial
contractility/ relaxation
 Vasodilation
 Antiplatet/ antiinflammatory?

44.  End stage disease
 Refractory to standard
therapy:
 Frusemide 4mg/kg POTID
 Pimobendan 0.25 mg/kg PO
BID
 Benazepril 0.25 mg/kg PO
SID

45.  Sleeping RR > 40 breaths/min
 Spironolactone 2 mg/kg bid
 Hydrochlorothiazide 1mg/kg 2x/week* -
2 mg/kg bid
 Pimobendan 0.3 mg/kgTID
 +/- antiarrhythmics (AF, SVT,VPCs)
 +/- hydralazine or amlodipine
 +/- sildenafil (only if severe PHT)
* Unpublished dose. Must monitor renal parameters

46.  Benazepril/ pimobendan
(Fortekor Plus)
 Benazepril/ spironolactone
(Cardalis)
 ‘Bespoke’ combinations
(frusemide/benazepril/pimobendan)

47.  Medical emergency
 Markedly dyspneac and hypoxemic
 Coughing white/blood tinged froth
 RR >100 breaths/min
 HANDLE GENTLY

48.  O2
 Baseline RR, body weight
 IV frusemide 4-6 mg/kg q30-60mins or
CRI till RR < 60 OR lost 10% BW
 Delay radiographs/ echocardiography
 Consider arteriolar dilators: oral
hydralazine, IV nitroprusside (BP)
 Positive inotropes: dobutamine or
pimobendan (single daily dose IV)

50.  Procedure of choice –
humans
 Replacement - potential
for thrombosis
 Lifelong anticoagulant
therapy
 Repair preferred

51. Difficult in dogs:
 Very few trained veterinarians
 AU ~ $30,000 - $60,000
 Requires cardiopulmonary bypass
 High mortality*
* Other than if performed by a single Japanese surgeon

52.  11 yo FS Poodle X
 Presented to me for
evaluation of a murmur
 12 months ago grade II/VI
 At presentation grade IV/VI
 Needs surgical evaluation of
left cranial cruciate rupture

53.  10 kg
 HR 100 bpm, PR 100 bpm
 Grade IV/VI left apical systolic murmur
 RR 24 breaths/minute
 Lame left hind
 Hx and PE consistent with MMVD

54. LA:Ao 1.63
LVIDd 3.7 (2.7-3.4)

55.  3 weeks lethargy
 Decreasing appetite
 RR 100 breaths/minute
 Soft gag/ cough
 HR 160 bpm
 Grade IV/VI murmur

57.  LA:Ao 2.4 (<1.5)
 LVIDd 4.28 (2.5-3.2)
 Severe MR
 MildTR
 MMVD stage C

58.  10 kg
 Frusemide 20 mg bid (2 mg/kg bid)
 Pimobendan 2.5 mg bid (0.25 mg/kg bid)
 Benazepril 2.5 mg sid (0.25 mg/kg sid)
 Renal profile 1 week later unremarkable
 BAR, RR 24, HR 120 bpm

59.  Presented to ICU quiet, inappetant
 RR 88 breaths/minute, cyanotic
 HR 230 beats, irregularly irregular
 O2
 Frusemide 4 mg/kg hrly till RR < 60
 Then 4 mg/kg 4 hrly
 ECG

60. Discharged on frusemide 30 mg bid, pimobendan
2.5 mg bid, benazepril 2.5 mg sid

61.  Recurrence of dyspnea
 Sinus rhythm
 Increased frusemide to 30 mg po tid
 Ebony doing well – owners reduced
frusemide to 20 mg bid
 ** DO NOT DOTHIS!!**

62.  5 months post initial presentation
 3 months post initial CHF
 Dyspnea
 Inappropriately reduced frusemide
 Medications 3 hrs late
 Disease progression
 RR 140 breaths/minute, dull, cynaotic
 HR 100*, marked pulm crackles
 No response to IV frusemide boluses
 Critical, cardiorespiratory arrest close

63.  O2
 Frusemide 6 mg/kg bolus IV
 CRI 3 mg/kg/hr
 Nitroprusside 5 ug/kg/min*
 Gradually improved over 12 hrs
 Weaned down overnight
 Both CRI’s discontinued after 24 hrs
 Frusemide 3 mg/kg IV q 3hr for 24 hrs
 Ventilation?
* Continuous BP monitoring essential

64.  Renal profile
 K+ 2.8 (3.5-5.8)
 BUN 22 (2.5-9.6)
 Creat 145 (22-159)
 Discharged
 Frusemide 30 mg POTID
 Pimobendan 2.5 mg PO BID
 Benazepril 2.5 mg PO SID
 Spironolactone 25 mg PO SID*
 Kgluc 4 mEq BID* * New medications

65.  CHF
 9.0 kg
 Frusemide 40 mgTID*
 Spironolactone 25 mg BID*
 + Hydrochlorothiazide 6.25 mg PO EOD
 2 weeks later – mildly increased RR
 BP 154 mm Hg
 + Amlodipine 2.5 mg po sid
* Maximum dose

66.  Stage D MMVD, 9 kg dog
 Frusemide 40 mg POTID
 Spironolactone 25 mg PO BID
 Hydrochlorothiazide 6.25 mg PO EOD
 Pimobendan 2.5 mg PO BID
 Amlodipine 2.5 mg PO SID
 Benazepril 2.5 mg PO SID
 Kgluc 4 mEq PO BID

67.  Stable for 3 months
 Represented 6 months post initialCHF
 Dyspnea (RR 60 breaths/minute)
 FrusemideCRI 1 mg/kg/hr
 Hydrochlorothiazide 12.5 mg PO sid
 Recheck 1 week later – 1st syncopal episode
 HR 120 bpm, RR 42 (stressed, post syncope),
mm pale

68.  Arrhythmia - tachy or bradyarrhythmia
 Severe MR - hypotension
 Recurrence of CHF
 Pulmonary hypertension
 Left atrial tear

69.  ECG – sinus tachycardia 150 bpm
 BP 80-100 mm Hg (systolic)
 Echocardiogram
 Severe MR: LA/Ao 3.0
 LVIDd 5.0 cm (2.5-3.1)
 Moderate pulmonary hypertension (TR PG 68 mm
Hg)
 No pericardial effusion (to suggest left atrial tear)

70.  Pulmonary arteriolar constriction
secondary to pulmonary venous
hypertension
 Exacerbates mild right heart
disease
 Cx – diuretic refractory ascites,
exercise intolerance, syncope
 Dx: PA cath (gold standard) or
echo (needTR or PI)
25
25
5

71.  Dyspnea
 Renal profile:
 BUN 76 (2.5-9.6)
 Creatinine 243 (44-159)
 Increased:
 Frusemide 40 mg qid
 Hydrochlorothiazide 25 mg am, 12.5 mg pm
 K+ 4 mEq bid
 Discontinue benazepril
 Thin body condition – Omega 3 FA’s

72.  RR 28 breaths/min
 Reducing appetite
 Syncope with exertion
 Current medications (8kg):
 Frusemide 40 mg po qid
 Pimobendan 2.5 mg po tid
 Spironolactone 25 mg po bid
 Hydrocholorthiazide 25 mg am, 12.5 mg pm
 Kgluc 4 mEq bid
 Amlodipine 2.5 mg sid

73.  Blood work
 BUN 36 (3.8-7.9)
 Creat 187 (44-159)
 BP: 105 mm Hg
 Echocardiogram
 LA:Ao 3.2
 LVIDd 5.15 (2.5-3.1)
 TRVmax 4.5 m/s, PG 85 mm Hg (severe PHT)
 + sildenafil 6.25 mg PO bid

74.  3 collapsing episodes today
 Subdued
 Inappetant and vomiting
 HR 160 bpm, weak pulses
 RR 60, moderate effort
 MM muddy grey
 Dull

75.  BP 88/40
 BUN 90 (2.5-9.6)
 Creat 240 (44-159)
 Dehydration vs renal failure?
 Treatment options:
 Stop frusemide
 IV fluids??

77. What now?