Hypertrophic Cardiomyopathy Flashcards
How is a clinical diagnosis of HCM made?
A clinical diagnosis of HCM is made on the basis of an end-diastolic wall thickness >= 15mm (6 sd above mean) in the absence of another cause of hypertrophy in adults. SAM of the mitral valve and hyperdynamic LV function are not required for a clinical diagnosis.
Which part of the left ventricle is most commonly affected in HCM?
The basal anterior septum in continuity with the anterior free wall
What morphological abnormalities can be part of the phenotypic expression of HCM?
- Hypertrophied and apically displaced papillary muscles
- Anomalous insertion of the papillary muscle directly into the anterior leaflet of the mitral valve
- Elongated mitral valve leaflets
- Myocardial crypts
- Myocardial bridging
- Right ventricular hypertrophy
What proportion of patients with HCM have a pathogenic or likely pathogenic genetic variant and what are the two most common gene variants identified in 70% of variant-positive patients?
- 30-60%
- Beta myosin heavy chain 7 (MYH7) and myosin-binding protein C3 (MYBPC3)
“Mutant sarcomere genes trigger myocardial changes, leading to hypertrophy and fibrosis, which ultimately results in a small, stiff ventricle with impaired systolic and diastolic performance despite a preserved LVEF”
What are the 6 main clinical features related to the pathophysiology of HCM?
- Dynamic LVOTO
- Mitral regurgitation
- Diastolic dysfunction
- Myocardial ischaemia
- Arrhythmias (VF/ VT, AF , WPW (associated with certain genotypes))
- Autonomic dysfunction
Among referral-based cohorts of patients with HCM, 30-40% will experience adverse events related to the above.
LVOT Obstruction:
What proportion of patients manifest LVOTO?
What are the two principal mechanisms responsible for LVOTO?
What peak gradient is considered indicative of obstruction and what gradient is considered be the threshold for septal reduction therapy for drug-refractory symptoms?
75% of patients manifest LVOTO at rest or with provocation (ESE > Valsalva).
Septal hypertrophy with narrowing of the LVOT leads to abnormal blood flow vectors that dynamically displace the mitral valve leaflets anteriorly. 2. Anatomic alterations in the mitral valve and apparatus, including longer leaflets and anterior displacement of the papillary muscles and mitral valve apparatus, which makes the valve more susceptible to abnormal flow vectors.
Peak LVOT gradient >= 30mm Hg is indicative of obstruction and resting or provoked gradients >= 50mm Hg = threshold for SRT for drug-refractory symptoms.
*By causing increased LV systolic pressure, LVOTO may exacerbate LVH, myocardial ischcaemia and prolong ventricular relaxation. LVOTO is associated with impaired stroke volume and an increased risk of HF and a poorer survival.
Mitral Regurgitation: What are the potential mechanisms of MR in HCM? How can these be clarified on echocardiography and why is it important to make the distinction?
MR can be from LVOTO and may therefore be dynamic. It can also arise from primary abnormalities of the leaflets / mitral valve apparatus. On echo, SAM of the mitral valve results in an MR jet that is predominantly mid to late systolic and posterior or lateral in orientation. Clarification of the mechanism is particularly important if septal reduction therapy is being contemplated to determine the optimal invasive approach.
What are the major advantages of surgical myectomy over ASA for treating symptomatic LVOTO?
- Lower rates of complete heart block
- Lower repeat procedure rates
- Concurrent treatment of mitral regurgitation (at the risk of increasing mortality and hospitalization)
- Concurrent surgical atrial fibrillation ablation
What are the important differential diagnoses for LVH in adults?
Anderson-Fabry disease, Friedrich ataxia, Danon disease, infiltrative disorders (amyloidosis, sarcoidosis, haemochromatosis), glycogen storage disorders.
What factors predict earlier onset of the HCM phenotype?
Why can the frequency of screening be reduced in adults > 18 years of age?
Males, family history of SCD, pathogenic variants in MYH7 / MYBPC3.
Phenotype conversion can occur in adulthood, but disease penetrance is lower in individuals > 18 years.
Screen all relevant family members at the time another family member is diagnosed. Adults can be screened every 3 to 5 years, but in children and adolescents the screening interval is more frequent.
What is the role of CMR in the management of HCM?
CMR can provide a more accurate measurement of LV wall thickness and identify areas of LVH not well visualized on echocardiography.
CMR can help exclude HCM-mimics
CMR can identify morphological abnormalities (LV apical aneurysms, structural abnormalities of the mitral valve and subvalvular apparatus) and quantify the extent of LGE (> 15% thought to confer 2-fold increase in SCD)
What are the established clinical risk factors for HCM Sudden Death Risk Stratification?
- Family history of sudden death definitively or likely attributable to HCM; greatest weighting given to first degree relatives <= 50 year
- Massive LVH – wall thickness >= 30mm in any segment
- Unexplained syncope that is unlikely to be vasovagal, nor attributable to LVOTO
- HCM with LV systolic dysfunction (LVEF < 50%)
- LV apical aneurysm defined as a discrete thin-walled, dyskinetic or akinetic segment of the most distal portion of the LV chamber, independent of size
- Extensive LGE on CMR imaging (> 15% of LV mass)
- NSVT on 24-48 hour ambulatory monitoring. Greater weight is placed on runs that are frequent >=3, longer >= 10 beats and faster (>= 200bm)
ESC calculator incorporates a number of disease-related features into a logistic regression equation to estimate 5 year SCD. Contemporary SCD risk markers including LV apical aneurysm, LGE and systolic dysfunction (EF < 50%) are not included in the risk calculator and their impact of the calculated 5 year risk estimate is uncertain.
*Note that genotype positive patients without LVH are not at an increased risk of SCD relative to the general population
Management of LVOTO:
- How should beta blockers be titrated?
- What are the limitations to using nondihydropyridine CCBs?
- What is the role of disopyramide, what are the important considerations in patients with AF, how can anti-cholinergic side effects be managed?
- According to symptoms and HR; you want to see a reduction in resting HR to ascertain there is adequate beta blockade.
- Diltiazem and verapamil have vasodilating properties which can be limiting
- Disopyramide can provide symptomatic relief in patients who have failed first line therapies, especially if they are not candidates for SRTs. It needs to be used with an AV nodal blocker in patients with AF since it increases conductivity through the AV node.
In patients with heart failure requiring diuretics or hypertension with symptomatic LVOTO, treatment of fluid retention / BP needs to be cautious. May also need to intensify treatment of LVOTO.
What types of ventricular arrhythmia occur in patients with HCM and how can these be managed?
Historical belief that the cause of SCD In patients with HCM was VF (this is still most common). Substantial proportion of patients have ventricular flutter / monomorphic VT.
ATP has been shown to be effective in ¾ cases of MMVT associated with HCM; MMVT is common in patients with apical aneurysms.
There is no data re use of AADs in patients with HCM – extension of OPTIC trial data where at 1 year, shocks occurred in 38.5% of patients assigned to beta blocker alone, 24.3% assigned to sotalol and 10.3% assigned to amiodarone plus beta blocker.
There is also a role for VT ablation although a large proportion of patients require combined endo and epicardial ablation.
What should be the approach to managing patients with HCM and reduced LVEF?
Why are LVADs generally unsuitable in patients with HCM?
Since HCM with reduced LVEF is rare, firstly need to exclude other causes of reduced LVEF including CAD, HCM mimics, severe MR.
Patients with HCM were usually excluded from HF trials, but it is generally accepted that GDMT can be trialed.
Small cavities and relatively normal LVEF have previously precluded the use of LVADs in patients with HCM.
