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Restrictive Cardiomyopathy


  • Aka Restrictive Pericarditis
    • Must differentiate from Constrictive Pericarditis (which is reversible)
  • Infiltrative Cardiomyopathies
  • Irreversible, myocardial problem
    • CHF w/LVH and normal ventricular chamber dimensions that may progress to dilated cardiomyopathy or may be thickened with granularity
  • Exam
    • Usually has pulmonary congestion
    • S3
    • Pericardial thickness <2mm
  • Labs
    • BNP markedly elevated (BNP normal to slightly elevated in Constrictive Pericarditis)
      • 600 typically

  • Diagnostics
    • EKG may be normal or low voltage
    • Atrial Fib early
    • PA systolic pressure >60
  • Treatment
    • Diuretics
    • Thoracotomy with Pericardiectomy

1) Amyloidosis


  • AL (Immunoglobulin Light-chain) Amyloidosis
  • ATTR (Transthyretin Amyloid) Amyloidosis
    • More common in men
    • Abnormal 99m-technetium pyrophosphate scan can be used to avoid biopsy to distinguish


  • Cardiac
  • Renal
    • Nephrotic syndrome
    • Peripheral edema
  • CNS
    • Peripheral and/or autonomic neuropathy
    • Stroke
  • GI
    • Hepatomegaly
    • Dysmotility, malabsorption
    • GI bleeding
  • Pulm
    • Pulmonary nodules, tracheobronchial infiltration, pleural effusions
  • MSK
    • Enlarged tongue, shoulder pad enlargement
  • Skin
    • Thickening of skin, subcutaneous nodules/plaques
    • Ecchymoses, periorbital purpura
  • Heme
    • Anemia
    • Thrombocytopenia

AL Cardiomyopathy


  • VT/VF
    • Much more common than in ATTR-CM

Transthyretin Amyloid Cardiomyopathy (ATTR-CM)


  • 5000-7000 cases annually, male predominance, hATTR is AD
    • 100 different mutations
    • Mc in USA is Val122Ile (3-4% of AA, 1.5m carriers)
    • Mc globally is Val30Met
  • Transthyretin amyloid cardiomyopathy is a rare but severe cause of restrictive cardiomyopathy, caused by the accumulation of transthyretin fibrils in the myocardium
    • Synthesized in the liver into 4 Beta-sheet-rich monomers that normally act as a carrier proteins for retinol and thyroxine
    • Misfolded transthyretin aggregates and preferentially deposits in the Myocardium and Peripheral nerves
    • Chromosome 18 carries the TTR protein gene
      • Mutations in gene coding can cause structural changes in TTR causing misfolding
        • Aka hATTR or hereditary ATTR
      • Misfolding due to normal aging is called wATTR or wild-type ATTR (more common)


  • CHF (fatigue/poor exercise tolerance/SOB)
  • Arrhythmia


  • 40-50% of ATTR have unrelated Monoclonal Gammopathy


  • Gold Standard: Endomyocardial biopsy with congo red staining
    • SN/SP 100% if ≥4 sites sampled
  • PYP and CMR
  • EKG: Low voltage with poor R wave progression in precordial leads
    • 25-40% of ATTR-CM patients
    • Different than normal LVH people who have large waves*
    • Pseudo-infarct pattern also reported
    • High voltage QRS pattern in Val122Ile possible
    • Abnormal mass/voltage ratio
      • Increased LV mass and low QRS voltage (<5mm in limb leads, <10mm in precordial leads)
        • Compare to strain pattern seen in LVH (increased QRS voltage), pericardial effusion (decreased QRS without LVH)
  • TTE: Bi-ventricular hypertrophy
    • Septal wall thickness of >12mm makes it a consideration
    • Increased echogenicity
    • Small LV, Biatrial enlargement, thickened interatrial septum, thickened valves
    • Diastolic dysfunction
  • Strain TTE: “Apical sparing” with progressive worsening longitudinal strain when moving to midventricular and basal segment is characteristic
    • “Bulls-eye”, “Cherry on top” pattern
    • Apical to basal strain ratio and apical to mid-ventricular plus basal strain1
  • CMR:
    • With late gadolinium enhancement (CMR-LGE)
      • Diffuse late mid-myocardial gadolinium enhancement in a noncoronary distribution
    • The presence of diffuse transmural or subendocardial deposits can diagnose amyloidosis with a sensitivity and specificity of 85 to 90%
    • Inability to "null" or suppress the myocardial signal on phase-sensitive inversion recovery (PSIR) imaging of LGE scan is also diagnostic
    • It is seen that T1 signals are amplified in cardiac amyloidosis, similar to post-contrast extracellular volume fraction (ECV)
    • CMR with parametric imaging can identify native (non-contrast) myocardial T1 signal and ECV
    • Parametric imaging is believed to be a more sensitive and reliable measure of amyloid burden, and therefore can be used for treatment tracking
  • Nuclear Imaging is only diagnostic imaging technique
    • TC-PYP is 100% specific when Grade 2-3 present
      • No need for biopsy
      • Myocardial uptake ≥ Bone
    • Heart to contralateral chest uptake ≥1.5 = ATTR
      • ≥1.6 ratio have worse 5-year outcomes
  • Genetic Testing after PYP or Biopsy
    • Differentiates hATTR from wATTR



  • Cardiomyopathy/Diastolic Dysfunction/Heart Failure/LVH
  • Peripheral Neuropathy
    • More commonly seen in hATTR than wATTR
    • Bilateral carpal tunnel syndrome
      • 50% of wATTR
      • Occurs 5-10 years before wATTR-CM
    • Lumbar stenosis
      • Spinal foraminal narrowing
  • Spontaneous tendon ruptures are not uncommon
    • 33% of wATTR-CM patients had spontaneous rupture of distal biceps tendon
  • Autonomic Dysfunction
    • Orthostatic hypotension
    • Erectile Dysfunction
    • Dyshidrosis
    • GI motility issues
    • More common in hATTR than wATTR
      • ACEI/ARB/BBs often poorly tolerated
  • Arrhythmias
    • More common in wATTR than hATTR
    • AFIB: 40-60% at time of diagnosis (usually persistent)
      • Often slow or controlled due to concomitant conduction disease
        • Leads to falls, syncope, falls
    • Conduction Disease
    • Ventricular Arrhythmias
      • Less common than in AL-CM
    • 33% require pacemakers eventually
  • Thrombosis
    • Irregardless of Afib status


  • hATTR-CM (2.5 years mean) worse than wATTR-CM (3.5 years mean)
  • hATTR w/polyneuropathy w/o CM (8-10 years mean)


  • CHF: Loops (Bumetanide/Torsemide) for volume
    • Avoid Verapamil
    • Midodrine + Compression stockings
  • Afib: Rhythm control to preserve atrial kick
    • Amiodarone preferred
    • Lifelong AC regardless of CHADs-VASc
  • Patisiran (Onpattro)/Inotersen (Tegsedi)
    • Block synthesis of mutated TTR proteins by mRNA silencing
    • Both approved for hATTR polyneuropathy w + w/o CM
  • Tafamidis (Vyndamax/Vyndaqul)
  • Diflusinal
    • Not FDA approved
    • Stabilizes TTR tetramer to prevent tissue deposition
      • Doxycycline + Tauroursodeoxycholic Acid
    • Removes deposited amyloid fibrils
  • Liver Transplant
    • Can be used for hATTR not wATTR

2) Sarcoid Cardiomyopathy

  • Diffuse Granulomatous involvement of the heart
  • Sarcoidosis of the heart

3) Hemochromatosis

4) Lipid Storage Diseases