Restrictive Cardiomyopathy
General¶
- 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
-
- BNP markedly elevated (BNP normal to slightly elevated in Constrictive Pericarditis)
- Diagnostics
- EKG may be normal or low voltage
- Atrial Fib early
- PA systolic pressure >60
- Treatment
- Diuretics
- Thoracotomy with Pericardiectomy
1) Amyloidosis¶
Types¶
- 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
Features¶
- Cardiac
- Restrictive cardiomyopathy
- Concentric ventricle thickening with diffuse fibril deposits
- Cardiac amyloidosis: a practical approach to diagnosis and management
- Conduction defects, low voltage
- Orthostatic hypotension
- Restrictive cardiomyopathy
- 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¶
Complications¶
- VT/VF
- Much more common than in ATTR-CM
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)¶
Etiology¶
- 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)
- Mutations in gene coding can cause structural changes in TTR causing misfolding
Symptoms¶
- CHF (fatigue/poor exercise tolerance/SOB)
- Arrhythmia
Labs¶
- 40-50% of ATTR have unrelated Monoclonal Gammopathy
Diagnosis¶
- 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)
- Increased LV mass and low QRS voltage (<5mm in limb leads, <10mm in precordial leads)
- 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
- With late gadolinium enhancement (CMR-LGE)
- 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
- TC-PYP is 100% specific when Grade 2-3 present
- Genetic Testing after PYP or Biopsy
- Differentiates hATTR from wATTR
Staging¶
- Mayo Clinic wATTR-CM System
- Stage I: 66 months
- Stage II: 42 months
- Stage III: 20 months
Complications¶
- Cardiomyopathy/Diastolic Dysfunction/Heart Failure/LVH
- TTR found in 20% of HF patients with myocardial wall thickening of more than 14mm
- More common in wATTR than hATTR
- Cardiorenal Syndrome typically ensues
- Often become BB and ACEI/ARB intolerant
- 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
- Often slow or controlled due to concomitant conduction disease
- Conduction Disease
- Ventricular Arrhythmias
- Less common than in AL-CM
- 33% require pacemakers eventually
- Thrombosis
- Irregardless of Afib status
Prognosis¶
- hATTR-CM (2.5 years mean) worse than wATTR-CM (3.5 years mean)
- hATTR w/polyneuropathy w/o CM (8-10 years mean)
Management¶
- 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)
- FDA approved for ATTR-CM
- 1B per ESC
- Reduces all-cause mortality and CV hospitalization in CHF I/II but takes 2 years
- Stabilizes TTR tetramer to prevent tissue deposition
- 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