Medical Management of Great Ape Cardiomyopathy - What We Do and Why We Do It - Great Ape Cardiomyopathy

Great Ape Cardiomyopathy

 Medical Management of
Great Ape Cardiomyopathy

  What We Do and Why We Do It

  Gregg
  Gregg Rapoport,
        Rapoport, DVM,
                  DVM, DACVIM
                       DACVIM (Cardiology)
                               (Cardiology)
           Assistant Professor of Cardiology

I. Cardiomyopathy - Classification

II. Great Ape Cardiomyopathy

III. Medical Management

Classification of Cardiomyopathies
    Definitions and Nomenclature

Cardiomyopathy
        Definition and Classification

cardiomyopathy - disease of the myocardium
associated with actual or potential cardiac dysfunction

primary cardiomyopathy - myocardial disease with no
identifiable systemic or structural intracardiac cause

secondary cardiomyopathy - myocardial disease
with an identifiable underlying cause
  e.g. thyrotoxic heart disease, taurine deficiency, valvular heart
  disease, systemic hypertension, infiltrative heart disease

Cardiomyopathy
Definition and Classification

The primary cardiomyopathies
  dilated cardiomyopathy
  hypertrophic cardiomyopathy
  restrictive cardiomyopathy
  arrhythmogenic right ventricular cardiomyopathy
  unclassified cardiomyopathy

Dilated Cardiomyopathy

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Restrictive Cardiomyopathy

                     Courtesy of Dr. Phil Fox (AMC)

Restrictive Cardiomyopathy

               Myocardial Form

Restrictive Cardiomyopathy

             Endomyocardial Form

Arrhythmogenic Right
Ventricular Cardiomyopathy

                     Courtesy of Dr. Phil Fox (AMC)

Arrhythmogenic Right
Ventricular Cardiomyopathy

                     Tong et al, Vet Pathol 2013

Tong et al, Vet Pathol 2013

Arrhythmogenic Right
Ventricular Cardiomyopathy

Great Ape Cardiomyopathy
   Where Does It Fit In?

Great Ape Cardiomyopathy

What does it look like?
→ one observed disease course...
   concentric left ventricular (LV) hypertrophy
   +/- (progression to?) LV systolic dysfunction
      if so → LV chamber dilation

   +/- progression to heart failure
   +/- other features (e.g., apical hypertrophy)
   +/- sudden death (at any stage)

Great Ape Cardiomyopathy

Big picture outcomes:
  pre-clinical / asymptomatic phase (duration?)

  sudden cardiac death
  congestive heart failure
  +/- other sequelae (e.g., thromboembolism)
  persistently asymptomatic

Great Ape Cardiomyopathy

Big picture questions:
  1° or 2°
  cardiomyopathy?
  one disease or multiple diseases?
  role of blood pressure?
     systemic hypertension?

  Name?
     how about...

Medical Management of
Great Ape Cardiomyopathy
  Why We Do What We Do

Myocardial Dysfunction

  Systolic     Diastolic

↓Cardiac Function

↑ Cardiac                        Neurohormonal
Workload         CHF                Activation
                                  (RAAS, SNS)

              Fluid Retention
              Vasoconstriction
                Tachycardia

Internal Carotids

                                           CN IX
External Carotids

                      Carotid
                       Sinus
                     Receptors
                                                     nucleus tractus solitarius
                                        Afferents

                      Aortic
                      Arch
                                           CN X
                    Receptors

                      Aortic Arch
                                         ARTERIAL
                                        BAROREFLEX

Internal Carotids

                                              CN IX
External Carotids

                      Carotid
                       Sinus
                     Receptors
                                              CO             nucleus tractus solitarius
                                          Afferents

                                                                    tachycardia

                      Aortic
                      Arch
                                              CN X                 increased
                                                                    systemic
                    Receptors                                       vascular
                                                                   resistance

                                                                   increased
                                                                      fluid
                                                                    retention
                      Aortic Arch
                                         ARTERIAL
                                        BAROREFLEX
                                        With Heart Disease

Concept:
Maladaptive Response to Heart Disease
    The body’s “cure” is part of the disease
          Progressive Heart Disease
                       ↓
             Relative Hypotension
                       ↓
                  Homeostasis
     (renin-angiotensin-aldosterone system,
          sympathetic nervous system)
                       ↓
                Tachycardia,
          VasoconstrictionProgressive
               Fluid Retention
              ↓
   CONGESTIVE HEART FAILURE

General Approach to
Management of Heart Disease/Failure
         Progressive Heart Disease
                      ↓
            Relative Hypotension
                      ↓
                 Homeostasis
    (renin-angiotensin-aldosterone system,
         sympathetic nervous system)
                      ↓
               Tachycardia,
         VasoconstrictionProgressive
              Fluid Retention
             ↓
  CONGESTIVE HEART FAILURE

CONGESTIVE HEART FAILURE

Cornerstones of Heart Failure Management:
  renin-angiotensin-aldosterone system blockade
    angiotensin-converting enzyme inhibitor (ACEI) preferred
    angiotensin II receptor blockers if ACEI not tolerated
    aldosterone antagonist if no contraindications

  beta-adrenergic receptor blockade

  diuretics

ACE inhibitors
  over 30 placebo-controlled human trials including
  over 7,000 patients
  all patients studied had LV systolic dysfunction
  (ejection fractions < 35-40%)
  overwhelmingly positive results
     improved symptoms of heart failure
     improved quality of life
     decreased risk of hospitalization for heart failure
     improved survival time
  class effect (all ACEIs studied were beneficial)

Beta blockers
  over 20 placebo-controlled human trials including
  over 20,000 patients
  all patients studied had LV systolic dysfunction
  (ejection fractions < 35-45%)
  similarly positive compared to ACEIs
  additive with ACEIs
     patients already receiving an ACEI still saw benefit
     basis for strong recommendation to use both if possible
  class effect

Statement made regarding use of beta blockers,
but safe to extrapolate to ACE inhibitors:
  "Beta blockers should be prescribed to all patients with stable heart
  failure due to reduced left ventricular ejection fraction unless they
  have a contraindication to their use or have been shown to be
  unable to tolerate treatment with these drugs. Because of the
  favorable effects of beta blockers on survival and disease
  progression, treatment with a beta blocker should be initiated as
  soon as left ventricular dysfunction is diagnosed. Even if symptoms
  are mild or have responded to other therapies, beta blocker therapy
  is important and should not be delayed until symptoms return or
  disease progression is documented during treatment with other
  drugs. Therefore, even if patients do not benefit symptomatically
  because they have little disability, they should receive treatment
  with a beta blocker to reduce the risk of disease progression, future
  clinical deterioration, and sudden death."

Diuretics
   short- and intermediate-term studies revealed:
      increased Na+ excretion and urine production
      decreased physical signs of fluid retention
      improved exercise tolerance
      improved LV performance (increased stroke volume)
   no long-term studies!
      unknown effect on morbidity or mortality for any diuretic,
      including furosemide, in the treatment of heart failure
   parachute study: don’t do it!

Smith et al, BMJ 2003

Statement made regarding use of diuretics:

“Diuretics should be prescribed to all patients who
have evidence of, and to most patients with a prior
history of, fluid retention. Diuretics should generally
be combined with an ACEI and a beta blocker. Few
patients with heart failure will be able to maintain
dry weight without the use of diuretics.”

SUMMAR
                      Y
Great ape cardiomyopathy ≠ model for other
known forms of heart disease
   caveat: role of systemic hypertension remains unknown

If we choose to extrapolate from human field:
   strong role for ACEIs and beta blockers for affected apes
   with heart disease that includes LV systolic dysfunction
   no proven benefit for any drug w/o LV systolic dysfunction
   (unless hypertension is confirmed)
   use diuretics when necessary (fluid retention)

Need more information about blood pressure in apes