Co-Chairs Milind Desai, MD, MBA, FACC, FAHA, FESC, and Andrew Willeford, PharmD, PhD, BCCP, prepared useful Practice Aids pertaining to hypertrophic cardiomyopathy for this CME/MOC/CPE/AAPA/IPCE activity titled “Adapting Managed Care Strategies in the Era of Precision Medicine for Hypertrophic Cardiomyopathy.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CPE/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4bb7eKc. CME/MOC/CPE/AAPA/IPCE credit will be available until May 16, 2025.

1. Screening and Diagnosing Suspected
Hypertrophic Cardiomyopathy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
Recommendations for Initial Clinical Evaluation and Testing Algorithm
for Patients With or Suspected of Having HCM1
Testing
ECG
Resting
obstruction
Echo
Provocable
obstruction
CMR
Nonobstructive
Identification of HCM phenotype (LVH)
Obstruction at rest
Stress echo
Yes No
HCM Suspected
Personal History
Symptoms
Physical
Exam
Family History
HCM diagnosis, sudden death
Describe HCM
• Treatable
condition
• Compatible with
normal life
expectancy
Genetic testing
Pathogenic
sarcomere mutation
(30% of patients)
Cascade testing of
family members
Identify
phenocopies
G+/P+ G+/P-
Surveillance for
LVH development

2. Screening and Diagnosing Suspected
Hypertrophic Cardiomyopathy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
1. Maron BJ et al. J Am Coll Cardiol. 2022;79:372-389. 2. Ommen SR et al. Circulation. 2020;142:e533-e557.
Cascade Screening and Longitudinal Follow-Up for HCM2
Selected HCM Genetic Screening Tests
• Invitae: invitae.com
– Hypertrophic Cardiomyopathy Panel (30-44 genes)
– Cardiomyopathy Comprehensive Panel (82-112 genes)
• GeneDx: genedx.com
– Hypertrophic Cardiomyopathy (HCM) Panel (42 genes)
– Cardiomyopathy Panel (102 genes)
• Blueprint Genetics: blueprintgenetics.com
– HCM Panel (92 genes)
– Cardiomyopathy Panel (217 genes)
HCM Suspected or Family Hx of HCM
Diagnostic testing
(ECG, imaging, genetic)
Phenotype negative Phenotype positive
Family with
known P/LP
variant?
Patient
has family
variant?
Further clinical
or genetic
testing is not
recommended
Reassess
variant
classification
Screening ECG and
echo (CMR if echo
is inconclusive) at
the intervals in the
table below
Treadmill or bike
exercise testing
• Stress echo if
gradient <50 mmHg
• CPET if considering
advanced HF therapies
Every 1-2 y or with change
in symptoms
Serial evaluation for clinical
status, SCD risk (if no ICD
present), or sooner with
change in symptoms
• Clinical assessment
• Echo
• Holter
Every 2-3 y
Treadmill
exercise or
cardiopulmonary
exercise testing
for assessment
of functional status
Every 3-5 y
CMR for SCD risk
assessment (if no ICD
present) or to evaluate
for any suspected
morphologic changes
Variant
= P/LP
Variant downgraded
to VUS
Asymptomatic Symptomatic
No
Yes
No
Yes or
unknown
Surveillance Interval
Initiation of Screening
Age of First-Degree Relative
Every 1-2 y
At the time of diagnosis in another
family member
Children and adolescents from genotype-positive
family and/or family with early onset HCM
Every 2-3 y
At any time after the diagnosis in the
family, but no later than puberty
All other children and adolescents
Every 3-5 y
At the time of diagnosis in another
family member
Adults
Screening Asymptomatic First-Degree Relatives of Patients With HCM
1
2
3
4 5
HCM Index Case Targeted Gene Testing
Disease-causing
P/LP variant
VUS, B/LB, or no
variant identified
Regular follow-up
See 2
Reclassified as
P/LP
Reclassified as
VUS or B/LB
Consider
second tier
testing in
proband if
no variant
is identified
Cascade genetic
testing in family
Clinical surveillance
in family
Variant
positive
Variant
negative
HCM
diagnosed
No evidence
of HCM
Regular evaluation
for variant
reclassification
See 4
Regular follow-up
See 2
Regular clinical
surveillance
See 5
Further clinical or
genetic testing
not recommended
See 3

3. Distinguishing Imaging Features
of Various Cardiomyopathies1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
1. Galluzzo A et al. Life. 2023;13:171.
Athlete’s Heart
Hypertensive
Cardiomyopathy
Fabry
Cardiomyopathy
Amyloidosis
Hypertrophic
Cardiomyopathy
Transthoracic
Echocardiography
• Harmonic, eccentric LVH
• Enlargement of all cardiac
chambers
• Concentric LVH
• LV wall thickness usually
<15 mm
• Concentric LVH
• PM hypertrophy
• RV hypertrophy
• Concentric LVH with
granular sparkling aspect
• High-degree diastolic
dysfunction
• Apical sparing at STE
• Asymmetric LVH
• Possible LVOT obstruction
Cardiac
Magnetic
Resonance
• Normal findings (ie,
harmonic LVH with no
LGE)
• LGE: mid-myocardium
(arrow) and epicardium
• LGE: typical basal
inferolateral mid-wall
(arrows); patchy areas
may be present
• LGE: subendocardial; in
ATTR possible transmural
pattern and RV
involvement (arrow)
• LGE: Frequent, often mid-
myocardial and epicardial
in the areas of maximal
LVH (arrows)

4. Recognizing and Treating Common Comorbidities
of Hypertrophic Cardiomyopathy1-8
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
Consequences
Prevalence
Comorbidity
• May increase LV mass, but rarely increases LV
thickness >16 mm
• HCM is accompanied by mitral valve abnormalities not
found in hypertensive cardiomyopathy
• Highly prevalent in the general population
• May also be present in patients with
unequivocal HCM
Hypertension
• Worsens hemodynamics of HCM, increases
symptom burden
• Reported in up to 70% of patients
with HCM
Sleep apnea
• Increases LV mass, more rapid clinical progression,
worsens HF symptoms, increases risk of AF
(especially in middle-aged adults)
• More common in HCM than in general
population
• oHCM observed in >50% with BMI >30
Obesity
• Major prognostic indicator, associated with increased
overall mortality, SCD, and cardiac events
• Myocardial ischemia is often observed in
patients with HCM
CAD
• Higher BMI, LA volume, and moderate-to-severe MR;
increased risk of AF events
• Common in HCM; more likely with MYH7
sarcomere variants
Atrial
fibrillation
Optimizing treatment of comorbidities can reduce symptom severity in patients with oHCM
Common Comorbidities of oHCM Encountered in Community Practice at Baseline
59%
35%
19%
9% 9% 9% 7% 6% 5%
HTN CAD DM CKD Syncope Vt/VF PAD MI Stroke
Proportion
of
Patients,
%
80
60
40
20
0

5. Recognizing and Treating Common Comorbidities
of Hypertrophic Cardiomyopathy1-8
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
a
The standards for control of modifiable CV risk factors should arguably recapitulate those used for secondary prevention in patients with CAD, in all genetic cardiomyopathies, based on the principle that superimposed ASCVD seems to have synergistic rather than additive effects.
b
1 RM corresponds to the maximum weight that can be lifted throughout the entire exercise movement only one time.
1. Finocchiaro G et al. J Am Heart Assoc. 2017;6:e007161. 2. Kramer CM et al. J Am Coll Cardiol EP. 2021;7:1376-1386. 3. Lee SP et al. Circ Heart Fail. 2018;11:e005191. 4. Marstrand P et al. Circulation. 2020;141:1371-1383. 5. Butzner M et al. Am J Cardiol. 2022;174:120-125.
6. Arbelo E et al. Eur Heart J. 2023;44:3503-3626. 7. Finocchiaro G et al. J Am Heart Assoc. 2017;6:e007161. 8. Cavigli L et al. Eur J Prev Cardiol. 2021;28:1093-1099.
Proposed Management of
Modifiable Risk Factors in
Patients With HCM
Possible Effects
Lifestyle/Clinical
Variable
↓ risk of CAD
↓ risk of MI
LDL <100 mg/dLa
↓ risk of secondary
LVH caused by
increased afterload
BP <130/80 mmHga
↑ diastolic function
↑ exercise capacity
↓ risk of obesity
Moderate exercise
↓ risk of obesity
↓ risk of development
of a more marked LVH
caused by increased
afterload
Weight
management
Key Recommendations for Exercise Prescription in HCM
• From 150-300 min/wk of low-to-moderate endurance exercise,
3-5 d/wk, depending on weekly volume
• All sessions must be preceded by a 5-min warm-up phase and end
with a 5-min cool-down
• Muscle-strengthening activities of low-to-moderate intensity that
involve all major muscle groups on 2 d/wk
• Flexibility training should be performed at least 2-3x/wk
(eg, stretching muscle groups 4x for 10-20 s each)
Frequency and
duration
• Low-to-moderate endurance training (training volume should be
emphasized more than intensity)
• Resistance training intensity should correspond to 40%-70% of 1 RMb
• Repetition set should be stopped before the point at which it would
be difficult to perform another repetition
Intensity
Tailor patient progression based on adaptation to exercise, previous
training experience, age, and clinical characteristics
Progression
• Start with a weekly session and introduce the second session when
the patient is adapted (optimal frequency is
3-4x/wk of endurance exercise)
Frequency
• Start with 10-30 min of endurance exercise and increase 10 min every
week to reach the optimal weekly training duration
(3-4 wk based on individual response to exercise)
Duration
• Start at low intensity during the first 3-4 wk, first increasing the volume
and then intensity
• Resistance exercises should start gradually with 1-3 sets of 8-10
exercises at slow-moderate velocity
Intensity

6. Considerations for Using Approved Cardiac Myosin
Inhibitors in the Management of HCM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
First-line
therapies
Advanced
therapies
Mavacamten2,3,a
(EXPLORER-HCM)
+
Yes
No
Still SRT eligible?
No
Yes
Disopyramideb
SRT willing?
Functional capacity improves with mavacamten
whether or not β-blockers are used4
Myectomy Myectomy or ablation
Ablation
Mavacamten3,5,a
(VALOR-HCM)
Re-evaluate
in 1-2 years
Symptoms with NYHA class III/IV or II with near
or exertional syncope on maximally
tolerated therapy?
β-blockade
Verapamil
or diltiazem
Treat comorbidities
Symptoms?
Avoid vasodilators
and diuretics
Other indication?
Yes
Yes
Yes
Yes
Yes
No
No
No
No
Surgical candidate?
Where Do Approved Cardiac Myosin Inhibitors Fit in the Management of oHCM?1-6

7. Considerations for Using Approved Cardiac Myosin
Inhibitors in the Management of HCM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
Suggested Multidisciplinary Approach to the Management of Mavacamten in oHCM7
This multidisciplinary workflow can efficiently address cost limitations for most patients
considering mavacamten. Use this template in your HCM center to initiate your own mavacamten program.
Physician assesses patient for initiation
with mavacamten
Pharmacist assesses drug interactions and
need for contraception
Pharmacist counsels patient using the REMS
brochure and enrolls patient into the REMS
program online
• Write initiation note
Pharmacist / Nurse enrolls patient into support
programs and submits prior authorization
Pharmacist checks approval and cost
Pharmacist discusses cost and sets treatment
start date with patient
Nurse / Echo Coordinator orders weeks 4, 8,
and 12 echos
• Use echo date calculator
• Create echo due date reminders
Pharmacist / Physician assesses
echo report
• Refer to PI for dosing
Pharmacist calls the patient
• Assess symptoms and adverse events
• Assess new drug interactions
• Submit REMS patient status form online
• Write note and submit prescription
Nurse / Echo Coordinator orders follow-up
echocardiograms
• Refer to PI for echo timing
• Use echo date calculator
Repeat
for
weeks
8
and
12
Repeat
for
all
subsequent
echos

8. Considerations for Using Approved Cardiac Myosin
Inhibitors in the Management of HCM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
Mavacamten: Examples of Known Drug-Drug Interactions8
Over-the-Counter Medications/Nutritional Supplements
Grapefruit juice
Esomeprazole
(Nexium)
Omeprazole
(Prilosec) St. John’s wort
Cimetidine
(Tagamet)
Prescription Medications
Clarithromycin
(Biaxin) Boceprevir
Fluconazole
(Diflucan)
Phenytoin
(Dilantin)
Apalutamide
(Erleada)
Felbamate
(Felbatol)
Telaprevir
(Incivek)
Etravirine
(Intelence)
Telithromycin
(Ketek)
Phenobarbital
(Luminal)
Fluvoxamine
(Luvox)
Mitotane
(Lysodren)
Primidone
(Mysoline) Nefazodone
Esomeprazole
(Nexium)
Ketoconazole
(Nizoral)
Ritonavir
(Norvir)
Posaconazole
(Noxafil)
Omeprazole
(Prilosec)
Fluoxetine
(Prozac)
Rifampin
(Rifadin)
Itraconazole
(Sporanox)
Efavirenz
(Sustiva)
Troleandomycin
(Tao)
Cimetidine
(Tagamet)
Carbamazepine
(Tegretol)
Ticlopidine
(Ticlid)
Bosentan
(Tracleer)
Voriconazole
(Vfend)
Nelnavir
(Viracept)
Enzalutamide
(Xtandi)
Idelasib
(Zydelig)
This is not a comprehensive list. For more information,
please refer to the full prescribing information.

9. Considerations for Using Approved Cardiac Myosin
Inhibitors in the Management of HCM
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DMR40
a
Mavacamten is a first-in-class cardiac myosin inhibitor that was FDA-approved after the 2020 AHA/ACC guidelines were published; for further information on this agent, please refer to its prescribing information.
b
AHA/ACC guidelines do not stipulate NYHA class or maximal therapy.
1. Ommen SR. ACC 2022. Oral presentation: 683-611. 2. Olivotto I et al. Lancet. 2020;396:759-769. 3. Camzyos (mavacamten) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214998s001lbl.pdf. 4. Wheeler MT et al. Eur J Heart Fail. 2022;25:260-270.
5. Desai MY et al. J Am Coll Cardiol. 2022;80:95-108. 6. Arbelo E et al Eur Heart J. 2023;44:3503-3626. 7. Willeford A et al. Circulation. 2023;148:A15539. 8. https://www.camzyosrems.com/assets/commercial/us/camzyosrems/en/pdf/Camzyos-REMS-Patient-Brochure.pdf.
9. https://www.cms.gov/medicare/coding-billing/icd-10-codes/2024-icd-10-cm.
oHCM Information Checklist for Mavacamten Approval Applications3,9
Use this checklist when working with the patient's insurance company to secure drug coverage
(eg, prior authorization, letter of medical necessity, letter of appeal). Always check with
the insurance company and their drug policies for specific requirements.
 Patient information (name, DOB, contact information, member ID, case #)
 ICD-10 code(s)
 oHCM: I42.1
 HF: Choose the appropriate code from the I50 code section
 Confirmation the patient is 18 years or older and not pregnant
 Patient's history and current condition (eg, symptoms associated with symptomatic oHCM, signs of oHCM observed
via echos, relevant comorbidities)
 Previous and/or current treatments for oHCM (eg, β blockers, CCBs)
 LVOT pressure documentation
 LVEF documentation
 Confirmation of no DDIs
 Confirmation the patient understands the requirements of and is enrolled in the REMS program
 Confirmation the provider and pharmacy are enrolled in the REMS program