01Approach to the Critical Patient/attcp52

Acute hemodynamic collapse

›Immediate recognition triggers

›Hypotension: SBP <90 mmHg in known or suspected HOCM

›Dynamic LVOTO worsens with decreased preload and afterload

›Vasodilators, diuretics, and positive inotropes are contraindicated

›Acute decompensation precipitants

›Dehydration or hemorrhage reducing preload

›Vasodilator administration (nitrates, ACE inhibitors, dihydropyridine CCBs)

›New-onset atrial fibrillation with rapid ventricular response

›Positive inotrope or vasopressor with beta-agonist activity (dopamine, dobutamine)

›Immediate stabilization steps

›IV fluid bolus for volume resuscitation

›Normal saline 500 mL IV bolus, repeat as needed to restore preload

›Passive leg raise as temporizing measure

›Trendelenburg positioning to augment venous return

›Vasopressor of choice: phenylephrine (pure alpha-1 agonist)

›Increases systemic vascular resistance without increasing HR or contractility

›IV infusion 100-200 mcg/min, titrate to MAP >65 mmHg

›Avoids worsening LVOTO unlike catecholamines

›IV beta-blocker for tachycardia or hyperdynamic state

›Metoprolol 2.5-5 mg IV slow push, repeat every 5 minutes PRN

›Target HR 50-60 bpm to prolong diastolic filling

›Conditions absolutely contraindicated in acute HOCM crisis

›Nitroglycerin and all nitrates

›Dobutamine and dopamine

›High-dose diuretics (furosemide)

›Dihydropyridine calcium channel blockers

02History/hx59

Presenting symptoms

›Cardinal exertional symptoms

›Exertional dyspnea: most common presenting symptom

›NYHA functional class I-IV stratification

›Reduced with rest and recumbency

›Exertional chest pain or pressure

›Microvascular ischemia and demand-supply mismatch mechanism

›Usually relieved with rest; may mimic angina

›Exertional presyncope or syncope

›Worsened by standing, dehydration, Valsalva maneuver, and heat

›Recent syncope within 6 months is a major SCD risk marker

›Palpitations

›Paroxysmal AF present in >50% at some point

›Ventricular ectopy or NSVT possible

›Postprandial symptom worsening

›Splanchnic vasodilation after large meals reduces preload

›Triggers LVOTO in susceptible patients

›Orthopnea and paroxysmal nocturnal dyspnea

›Suggests elevated filling pressures or congestive phase

Alarm features requiring urgent evaluation

›Syncope without prodrome or exertional syncope

›High-risk for arrhythmic SCD

›Distinguish from vasovagal by circumstance and recovery pattern

›Cardiac arrest or ICD shock

›ICD shock history implies high arrhythmia burden

›Interrogate device if available

›Progressive dyspnea at rest or NYHA class III-IV

›May indicate end-stage burned-out phase with LVEF <50%

03Physical Exam/exam44

Dynamic murmur assessment

›Characteristic murmur of HOCM

›Harsh crescendo-decrescendo systolic murmur

›Best heard at left lower sternal border and apex

›Dynamic character distinguishes from fixed obstruction

›Maneuvers that increase murmur intensity (increase obstruction)

›Valsalva maneuver (decreases venous return)

›Standing from squatting (reduces preload)

›Dehydration

›Maneuvers that decrease murmur intensity (decrease obstruction)

›Squatting from standing (increases preload and afterload)

›Passive leg raise

›Hand grip (increases afterload)

›Mitral regurgitation murmur

›Holosystolic murmur at apex radiating to axilla

›Due to SAM-mediated incomplete mitral valve closure

›Moves in same direction as outflow murmur with maneuvers

Cardiovascular examination

›Pulse characteristics

›Brisk bifid (bisferiens) carotid pulse

›Double-peaked systolic waveform due to dynamic obstruction

›Contrasts with slow-rising pulse of fixed aortic stenosis

›Arterial pulse amplitude and regularity

›Irregular pulse suggests AF

›Apical impulse

›Forceful, sustained, double-impulse or triple-impulse apical beat

›Lateral displacement with LV dilation in end-stage phase

›Heart sounds

04Differential Diagnosis/ddx36

Life-threatening diagnoses

›Aortic stenosis (ICD-10: I35.0)

›Fixed obstruction: murmur does not change with preload/afterload maneuvers

›Slow-rising carotid upstroke (pulsus parvus et tardus)

›Murmur decreases with Valsalva (opposite of HOCM)

›Calcified valve on echocardiography

›Acute coronary syndrome (ICD-10: I24.9)

›Troponin elevation, ECG ST changes

›HOCM can cause demand ischemia and ECG changes mimicking ACS

›Coronary angiography may be required to exclude concomitant CAD

›Hypertensive emergency with acute LVH (ICD-10: I16.1)

›Severe uncontrolled hypertension as precipitant

›LVH rarely exceeds 20 mm in pure hypertension

›No SAM or dynamic LVOTO on echo

Structural and genetic cardiomyopathies

›Hypertensive heart disease (ICD-10: I11.9)

›Concentric LVH pattern, rarely >20 mm wall thickness

›Requires sustained uncontrolled hypertension

›No SAM, no dynamic LVOTO, no family history of HCM

›Athlete's heart (ICD-10: Z87.39)

›Physiologic LVH, typically concentric, wall thickness <=13 mm

›Normal or supranormal diastolic function

›Regresses with 3 months of detraining

›No obstruction, no SAM, normal genetic testing

›Cardiac amyloidosis (ICD-10: E85.4)

›Biventricular wall thickening with low voltage on ECG (mismatch pattern)

›Apical sparing pattern on GLS strain imaging

›Congo red staining positive on biopsy; serum/urine protein electrophoresis

05Laboratory Tests/lt33

Cardiac biomarkers

›BNP or NT-proBNP

›Elevated with symptomatic heart failure or elevated filling pressures

›Useful for monitoring disease progression and treatment response

›NT-proBNP >900 pg/mL associated with worse outcomes

›Troponin I or T (high-sensitivity)

›Mild chronic elevation common due to myocyte disarray and fibrosis

›Acute significant rise warrants exclusion of concomitant ACS

›Correlates with extent of LGE on CMR

Metabolic and renal panel

›Basic metabolic panel

›Renal function: creatinine and GFR for medication dosing and diuretic safety

›Electrolytes: potassium monitoring essential with diuretics and disopyramide

›Glucose: metabolic comorbidity screening

›Thyroid-stimulating hormone

›Thyrotoxicosis exacerbates tachycardia and worsens LVOTO

›Hypothyroidism affects heart rate control response to beta-blockers

›Complete blood count

›Anemia as contributor to exertional symptoms and demand ischemia

›Baseline before anticoagulation in AF

Genetic and specialized testing

›Sarcomere gene panel

›8 sarcomere genes associated with HCM; MYH7 and MYBPC3 most common

›Pathogenic variants identified in 30-60% of clinically diagnosed HCM

›Genetic counseling mandatory before testing

›Positive result enables cascade screening of first-degree relatives

›Phenocopy exclusion labs when indicated

›Alpha-galactosidase A enzyme assay (Fabry disease screening)

06Diagnostic Tests/dt110

Scoring Systems

›HCM Risk-SCD calculator (ESC model)

›Five-year SCD risk estimation using 8 clinical variables

›Age, family history of SCD, unexplained syncope, LVOT gradient

›LA diameter, LV wall thickness, NSVT on Holter, LVEF

›Score <4%: ICD not generally recommended

›Score 4-6%: ICD may be considered (Class IIb)

›Score >=6%: ICD should be considered (Class IIa)

›Validated in European HCM cohorts; less studied in North American populations

›2024 AHA/ACC individual risk marker strategy

›Major SCD risk markers (each independently justifies ICD discussion)

›Prior cardiac arrest or sustained VT

›Family history of HCM-related SCD in first-degree relative

›Unexplained syncope within 6 months

›LV wall thickness >=30 mm

›LV apical aneurysm

›LVEF <50%

›Extensive LGE >=15% LV mass on CMR

›NSVT on Holter as additional risk factor for ICD consideration

›NYHA Functional Classification

›Class I: no symptoms with ordinary activity

›Class II: symptoms with moderate exertion

›Class III: symptoms with mild exertion, marked limitation

›Class IV: symptoms at rest or with minimal activity

MRI

›Cardiac MRI (CMR) with gadolinium

›Gold standard for LV wall thickness measurement (superior to echo)

›Identifies distribution: asymmetric septal, concentric, apical, or diffuse

›Measures maximum wall thickness at end-diastole

›Late gadolinium enhancement (LGE) assessment

›LGE >=15% LV mass: major SCD risk marker, Class IIa ICD indication

›Patchy mid-wall or replacement fibrosis pattern characteristic of HCM

›Absent LGE associated with better prognosis

›LV apical aneurysm detection

›Often missed by transthoracic echo; CMR preferred

›Associated with very high SCD risk and thrombus formation

›Tissue characterization for HCM phenocopy differentiation

›Amyloid: diffuse subendocardial LGE, myocardial nulling abnormality

›Fabry: inferolateral mid-wall LGE pattern without fibrosis

›Repeat surveillance every 3-5 years or sooner if clinical concern

›Functional assessment: LVEF, diastolic function, mitral regurgitation quantification

›CMR contraindications and alternatives

›Incompatible implanted devices or severe claustrophobia: cardiac CT alternative

›eGFR <30 mL/min/1.73m2: gadolinium use requires risk-benefit discussion

CT

›Cardiac CT angiography

›Alternative to CMR when CMR is contraindicated

›Incompatible ICD/pacemaker without MRI-conditional designation

›Severe claustrophobia unresponsive to anxiolysis

›Coronary anatomy assessment

›Myocardial bridging: systolic compression of coronary artery, present in ~30-40% of HCM

›Concomitant obstructive CAD exclusion before septal reduction therapy

›Preprocedural planning for alcohol septal ablation or surgical myectomy

›Delineates septal anatomy, coronary branching, and mitral valve morphology

›Structural assessment

›LV wall thickness and distribution

›LV outflow tract anatomy and dimensions

›Mitral valve and subvalvular apparatus evaluation

›CT limitations in HOCM

›No dynamic assessment of LVOT gradient

›Radiation exposure relevant for young patients requiring serial imaging

›No tissue characterization equivalent to LGE on CMR

Ultrasound

›Transthoracic echocardiography (TTE)

›Diagnostic criterion: maximal LV end-diastolic wall thickness >=15 mm

›>=13 mm diagnostic with positive family history or pathogenic genotype

›Exclude secondary causes (hypertension, aortic stenosis, athlete's heart)

›LVOT gradient measurement

›Resting gradient >=30 mmHg: obstructive physiology

›Resting gradient >=50 mmHg: threshold for septal reduction therapy consideration

›Dynamic: gradient changes >20 mmHg between rest and provocation

›Provocation for latent obstruction

›Valsalva maneuver during TTE to unmask latent LVOTO

›Exercise stress echocardiography: preferred for provokable gradients <30 mmHg at rest

›Amyl nitrite inhalation as alternative provocation

›Systolic anterior motion (SAM) of mitral valve

›Mitral leaflet contact with interventricular septum causes obstruction

›Severity graded by duration of contact and gradient produced

›Additional TTE parameters

›LVEF and diastolic function assessment

›Left atrial size: dilated LA predicts AF risk

›Mitral regurgitation severity and mechanism

›Pulmonary artery systolic pressure estimation

›Transesophageal echocardiography (TEE)

›Intraoperative guidance for surgical myectomy

›Detailed mitral valve anatomy before septal reduction therapy

›Assessment for intracardiac thrombus before cardioversion in AF

›Point-of-care ultrasound in the emergency setting

›Identify hyperdynamic LV with small cavity in acute hypotension

›End-systolic obliteration of LV cavity suggests severe LVOTO or depletion

›SAM visible in parasternal long-axis view

›Differentiate from other causes of shock: tamponade, RV failure, dilated CMP

›Ambulatory monitoring and functional testing

›24-48 hour Holter monitor or >=2-week wireless patch

›Detection of NSVT (SCD risk marker)

›Paroxysmal AF identification

›Cardiopulmonary exercise testing (CPET)

›Objective functional capacity assessment when symptom-exercise mismatch

›Peak VO2 <20 mL/kg/min suggests significant functional limitation

›Exercise stress echocardiography

›Provoke latent LVOTO in symptomatic patients with resting gradient <30 mmHg

›Induced gradient >=50 mmHg with exercise supports septal reduction therapy eligibility

›12-lead ECG

›Abnormal in 90-95% of HCM patients

›LV hypertrophy voltage criteria (Sokolow-Lyon, Cornell)

›Prominent Q waves in inferior and lateral leads (septal depolarization)

›ST-segment depression and T-wave inversions in lateral leads

›Left axis deviation and P-wave abnormalities (left atrial enlargement)

›Giant negative T waves in precordial leads: apical variant HCM

›Normal ECG present in only 5-10% of HCM cases

›High-risk ECG patterns

›Sustained or nonsustained ventricular tachycardia

›Pre-excitation (Wolff-Parkinson-White) associated with some HCM subtypes

›Wide complex tachycardia requiring urgent assessment

07Disposition/dispo33

Admission indications

›Criteria for hospital admission

›Acute hemodynamic instability or hypotension from LVOTO

›New cardiac arrest or sustained ventricular arrhythmia

›Syncope with suspected arrhythmic or hemodynamic etiology

›New-onset rapid AF causing hemodynamic compromise

›Acute decompensated heart failure with NYHA class III-IV symptoms

›Post-septal reduction therapy (myectomy or alcohol septal ablation)

›New diagnosis requiring inpatient workup and risk stratification

ICU-level care criteria

›Indications for ICU admission

›Refractory hypotension requiring vasopressor support

›Post-cardiac arrest resuscitation

›Intubated patient or impending respiratory failure

›Continuous arrhythmia requiring titrated IV antiarrhythmic therapy

›Cardiogenic shock with end-organ dysfunction

Observation and monitoring

›Observation unit criteria (12-24 hours)

›Presyncope with borderline hemodynamics now stable

›New AF with controlled rate and uncertain stability

›Symptomatic exacerbation requiring medication adjustment

›Holter monitor initiation for SCD risk stratification

Discharge criteria

›Safe discharge requirements

›Stable vital signs without vasopressor support

›No syncope, sustained arrhythmia, or acute hemodynamic instability

›Identifiable and correctable precipitant (dehydration, medication non-adherence)

›Adequate oral intake confirmed

08Treatment/t137

Acute medical management (ED setting)

›Volume resuscitation for preload-dependent hypotension

›Normal saline 0.9% 500 mL IV bolus

›Repeat boluses as needed to maintain MAP >65 mmHg

›Avoid excessive fluid if congestive failure present

›Passive leg raise for immediate preload augmentation

›Reversible and diagnostic maneuver

›Positive response (BP rise >=10 mmHg) confirms preload dependence

›Vasopressor therapy: phenylephrine first-line

›Phenylephrine IV infusion

›Starting dose 100 mcg/min IV infusion

›Titrate by 50 mcg/min every 5-10 minutes

›Target MAP >65 mmHg

›Maximum 300-400 mcg/min

›Pure alpha-1 agonist: increases SVR without inotropy or chronotropy

›Vasopressin as alternative

›0.03-0.04 units/min IV for refractory hypotension

›No direct cardiac contractile or chronotropic effect

›IV beta-blockade for acute rate/contractility control

›Metoprolol tartrate IV

›2.5-5 mg IV slow push over 2 minutes

›Repeat every 5 minutes to maximum 15 mg

›Target HR 50-60 bpm

›Esmolol IV for rapid titration

›Loading dose 500 mcg/kg IV over 1 minute

›Maintenance 50 mcg/kg/min

›Titrate 25-50 mcg/kg/min every 5-10 minutes

›Maximum 200-300 mcg/kg/min

›Ultra-short acting: half-life 9 minutes; easily reversible

Chronic pharmacologic management (per 2024 AHA/ACC Guidelines)

›First-line: nonvasodilating beta-blockers

›Metoprolol succinate (extended release) oral

›Starting dose 25-50 mg daily

›Titrate to resting HR 50-60 bpm

›Maximum dose 200-400 mg daily

›Class I recommendation per 2024 AHA/ACC guidelines

›Propranolol oral

›Starting dose 20-40 mg three times daily

›Titrate to HR target; maximum 480 mg daily

›Lipophilic; useful if concurrent migraine prophylaxis needed

›Nadolol oral

›Starting dose 40 mg daily

›Titrate to HR 50-60 bpm; maximum 160 mg daily

›Once-daily dosing: better adherence

›Second-line: nondihydropyridine calcium channel blockers

›Verapamil oral

›Starting dose 40-80 mg three times daily

›Maximum dose 480 mg daily

›Negative inotrope and chronotrope; reduces LVOTO

›Avoid combining with beta-blockers (additive AV block risk)

›Diltiazem oral

›Starting dose 30-60 mg four times daily (or extended release equivalent)

›Maximum dose 360-480 mg daily

›Preferred over verapamil in some patients with constipation risk

›Caution: initiation of verapamil in severe outflow obstruction and pulmonary hypertension

›Vasodilatory properties may precipitate hemodynamic collapse

›Start low; inpatient initiation if high gradient

Cardiac myosin inhibitors

›Mavacamten (Camzyos) - FDA approved 2022

›Mechanism: selective allosteric inhibitor of cardiac myosin ATPase

›Reduces hypercontractility and decreases LVOT gradient

›Improves symptoms and exercise capacity (EXPLORER-HCM trial)

›Indication: symptomatic obstructive HCM (NYHA class II-III) with gradient >=50 mmHg

›Starting dose 2.5 mg orally once daily

›Dose titration based on LVOT gradient and LVEF at weeks 4, 8, 12

›Maximum dose 15 mg daily

›Monitoring requirements

›LVEF must remain >=50%; reduce or hold if LVEF <50%

›Requires REMS program enrollment (REMS: Risk Evaluation and Mitigation Strategy)

›Strong CYP2C19 inhibitors/inducers affect drug levels significantly

›Class IIa recommendation per 2024 AHA/ACC guidelines

›Aficamten (Myqorzo) - FDA approved 2025

›Newer cardiac myosin inhibitor with more predictable pharmacokinetics

›SEQUOIA-HCM trial: superior to placebo for symptom improvement and gradient reduction

›ACAMARA trial (2025): aficamten monotherapy non-inferior to metoprolol for gradient reduction

›Starting dose 5 mg orally once daily

›Titrate based on echocardiographic response every 4 weeks

›Maximum dose 20 mg daily

›Less CYP2C19 drug interaction concern compared to mavacamten

Disopyramide

›Mechanism: class Ia antiarrhythmic with strong negative inotropic effect

›Reduces LVOT gradient by decreasing LV contractility

›Used as add-on to beta-blockers or CCBs for refractory obstruction

›Dosing

›Starting dose 100-150 mg orally four times daily

›Titrate to symptom response; maximum 400 mg four times daily

›Must be combined with AV nodal blocker (beta-blocker or CCB)

›Vagolytic effect of disopyramide can accelerate AV conduction in AF

›Risk of rapid ventricular response if used without AV nodal blocker

›Monitoring

›QTc interval: hold if >500 ms (torsades risk)

›Anticholinergic side effects: urinary retention, dry mouth, constipation, blurred vision

›Not recommended in patients with urinary outflow obstruction

Septal reduction therapy

›Surgical septal myectomy

›Gold standard septal reduction procedure

›Removes obstructing portion of basal interventricular septum

›Performed at experienced HCM centers (>20 cases/year)

›Indications: resting or provoked LVOT gradient >=50 mmHg

›NYHA class III-IV symptoms despite maximal medical therapy

›Class I recommendation per 2024 AHA/ACC at experienced centers

›Outcomes: >95% procedural success rate; 30-day mortality <1% at experienced centers

›Preferred when concomitant cardiac surgery required (MV repair, CABG)

›Alcohol septal ablation (ASA)

›Catheter-based percutaneous procedure

›Targeted ethanol injection into first septal perforator branch

›Creates controlled septal infarction to reduce obstruction

›Indications: suitable candidates who are high surgical risk or prefer percutaneous approach

›Outcomes: gradient reduction comparable to myectomy; higher complete heart block risk

›Complete heart block requiring permanent pacemaker in 10-20%

›Procedure-related MI size larger than myectomy

›Class IIa recommendation at experienced HCM centers

SCD prevention

›ICD implantation: secondary prevention

›Prior cardiac arrest or sustained VT: Class I recommendation for ICD

›Strong absolute indication regardless of other risk factors

›Transvenous ICD preferred for pacing capability and antitachycardia pacing

›ICD implantation: primary prevention

›One or more major risk markers: ICD reasonable (Class IIa)

›Unexplained syncope, wall thickness >=30 mm, family history of HCM-SCD

›LV apical aneurysm, LVEF <50%, LGE >=15% LV mass

›Reassess SCD risk every 1-2 years

›Subcutaneous ICD (S-ICD) considerations

›Alternative when transvenous lead placement complicated

›Cannot provide antitachycardia pacing or pacing for bradycardia

›T-wave oversensing more common in HCM due to voltage criteria

Atrial fibrillation management

›Anticoagulation: mandatory for all HCM patients with AF

›Regardless of CHA2DS2-VASc score (Class I recommendation)

›HCM itself confers high cardioembolic risk

›DOAC preferred over warfarin for non-valvular AF

›Apixaban 5 mg twice daily or rivaroxaban 20 mg daily with evening meal

›Dabigatran 150 mg twice daily as alternative

›Rate control

›Beta-blocker: metoprolol succinate 25-200 mg daily

›Nondihydropyridine CCB: verapamil or diltiazem if beta-blocker not tolerated

›Avoid digoxin: mild positive inotrope worsens LVOTO

›Rhythm control preferred for symptomatic AF in HCM

›Amiodarone: most effective antiarrhythmic for AF maintenance of sinus rhythm

›Loading 400 mg twice daily for 2-4 weeks, then 200 mg daily maintenance

›Monitor for pulmonary toxicity, thyroid dysfunction, hepatotoxicity

›Catheter ablation: reasonable for AF refractory to antiarrhythmic drugs

›Pulmonary vein isolation; higher recurrence rates in HCM due to LA fibrosis

›Disopyramide: antiarrhythmic useful for both AF and LVOTO (dual benefit)

09Special Populations/sp85

Pregnancy

›Hemodynamic changes in pregnancy affecting HOCM

›Blood volume increases 40-50% during pregnancy

›Increased preload generally beneficial for LVOTO in early pregnancy

›Third trimester: increased HR and reduced SVR may worsen obstruction

›Labor and delivery: highest hemodynamic risk period

›Valsalva during pushing dramatically increases LVOT gradient

›Blood loss during delivery reduces preload acutely

›Risk stratification in pregnancy

›Most women with HCM tolerate pregnancy well with appropriate monitoring

›Modified WHO classification III-IV if severe obstruction, syncope history, or NYHA III-IV

›Maternal and fetal risk assessment at HCM center or specialized cardiac obstetric clinic

›Medication safety in pregnancy

›Beta-blockers (metoprolol, propranolol): generally safe; Category B/C

›Neonatal bradycardia and hypoglycemia monitoring required

›Continue throughout pregnancy; do not abruptly discontinue

›Verapamil: Category C; use with caution; avoid if left heart failure

›Disopyramide: Category C; case reports of uterine contractions; avoid if possible

›Mavacamten and aficamten: contraindicated in pregnancy (teratogenicity unknown)

›Warfarin: avoid in first trimester (teratogenic); DOACs contraindicated in pregnancy

›Heparin or LMWH preferred anticoagulation for AF in pregnancy

›Delivery planning

›Vaginal delivery preferred in most cases with epidural anesthesia

›Epidural reduces afterload; careful titration required to avoid hypotension

›IV fluid preloading before epidural to prevent preload reduction

›Cesarean delivery reserved for standard obstetric indications

›Avoid oxytocin bolus doses (vasodilatory effect); use slow IV infusion instead

›Genetic counseling in pregnancy

›50% autosomal dominant transmission risk to offspring

›Prenatal genetic testing discussion with maternal-fetal medicine

Geriatric

›Age-related phenotype differences

›Older patients more likely to have coexisting hypertension and aortic stenosis

›Mixed physiology: HOCM plus fixed outflow obstruction

›Careful echocardiographic differentiation required

›Increased incidence of AF with aging in HCM population

›End-stage burned-out phase more common in older patients

›LVEF declines below 50% with fibrosis progression

›Medication considerations in older adults

›Beta-blockers: start low, titrate slowly; risk of falls from bradycardia

›Metoprolol 12.5-25 mg daily starting dose in frail elderly

›Verapamil: constipation and drug interactions (CYP3A4) more problematic

›Disopyramide: anticholinergic burden unacceptable in older adults

›Urinary retention, cognitive effects, constipation

›Avoid in patients aged >=75 years or those with cognitive impairment

›Anticoagulation in AF: bleeding risk vs. stroke prevention with validated tools (HAS-BLED)

›DOACs preferred; dose reduction criteria apply (apixaban 2.5 mg twice daily if two of: age >=80, weight <=60 kg, creatinine >=133 umol/L)

›SCD risk in elderly HCM

›Annual SCD risk lower in older patients than in younger patients

›ICD benefit vs. complication risk (lead failure, device infection, inappropriate shocks) carefully weighed

›S-ICD not suitable if pacing required for bradycardia (common in elderly)

›Functional assessment

›Frailty assessment: Clinical Frailty Scale or SPPB score

›Gait speed and fall risk relevant to anticoagulation and ICD decisions

›Septal reduction therapy: surgical risk significantly higher; ASA preferred in high-risk surgical candidates

Pediatrics

›Presentation in children and adolescents

›Often detected via family screening of first-degree relatives

›Screening recommended for children of affected parents starting age 10-12 years

›Earlier if symptoms, high-risk variant, or planning competitive athletics

›ECG and echocardiogram every 1-3 years during growth

›Sudden cardiac arrest during sports: HCM most common cause in US athletes <35 years

›Diagnosis in pediatric patients

›LV wall thickness z-score >=2 (adjusted for body surface area) diagnostic

›Adult absolute threshold (15 mm) may not apply in small children

›Consider syndromic causes: Noonan syndrome, LEOPARD syndrome, mitochondrial disease

›Associated features: short stature, dysmorphic facies, ptosis

›SCD risk stratification in pediatrics

›Higher overall SCD risk per year compared to adult HCM cohorts

›Risk markers: unexplained syncope, NSVT, wall thickness z-score >=20, family history of HCM-SCD

›ICD in pediatrics: shared decision-making with family

›S-ICD preferred in children to avoid transvenous leads during growth

›Device complications (inappropriate shocks) proportionally higher in children

›Athletic participation and restriction

›Historically: exclusion from competitive sports recommended

›2024 AHA/ACC guidelines: shared decision-making approach

›Individualized risk discussion replacing blanket restriction

›Informed consent documenting SCD risk discussion

›Avoidance of competitive sports with intense anaerobic bursts (basketball, football) still generally advised in high-risk phenotypes

›Medication dosing in children

›Propranolol: 0.5-1 mg/kg/day divided three times daily

›Maximum 4-6 mg/kg/day

›Verapamil: 3-5 mg/kg/day divided three times daily

›Avoid in children <1 year (fatal hemodynamic collapse reported)

›Mavacamten and aficamten: not approved for pediatric use; clinical trials ongoing

›Genetic testing in pediatric HCM

›Pathogenic sarcomere variant guides cascade screening of first-degree relatives

›Genetic counseling for parents regarding inheritance and reproductive implications

10Background/b87

Epidemiology

›Prevalence and incidence

›Most common inherited cardiac disease: prevalence approximately 1 in 500 in general population

›Estimated 750,000 individuals affected in the United States

›Worldwide prevalence consistent across ethnicities and races

›Autosomal dominant inheritance; de novo mutations occur

›Equal sex distribution in genotype-positive individuals

›Males more likely to develop obstructive physiology and severe symptoms

›LVOTO prevalence

›Two-thirds of HCM patients have LVOTO at rest or with provocation

›Resting obstruction (gradient >=30 mmHg) in approximately one-third

›Latent obstruction (induced only with provocation) in additional one-third

›Mortality and complications

›Annual SCD rate approximately 1% in general HCM population (pre-ICD era)

›Contemporary ICD era: SCD rate reduced to approximately 0.1-0.2%/year with appropriate treatment

›Leading cause of SCD in competitive athletes aged <35 years in the United States

›Most patients achieve normal or near-normal longevity with appropriate management

›AF develops in >50% of HCM patients over lifetime

›Stroke risk 4-6 times higher than general population due to AF

›Prognosis by phenotype

›Obstructive HCM: higher symptom burden; better targets for therapy

›Non-obstructive HCM: LVOT gradient <30 mmHg at rest and with provocation

›End-stage (burned-out) phase: LVEF <50%, develops in 2-5% of HCM patients

›Apical variant HCM: distinct morphology; lower SCD risk but high AF and thrombus risk

Pathophysiology

›Genetic basis

›Mutations in sarcomere protein genes encoding thick and thin filament components

›MYH7: beta-myosin heavy chain gene (most common)

›MYBPC3: myosin-binding protein C gene (most common)

›Less common: TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC1

›Pathogenic variants identified in 30-60% of clinically diagnosed patients

›Genetic heterogeneity: same mutation can produce different phenotypes within families

›Dynamic left ventricular outflow tract obstruction

›Systolic anterior motion (SAM) of anterior mitral leaflet

›Venturi and drag effects during systole pull leaflet anteriorly

›Leaflet contacts interventricular septum, causing obstruction

›Magnitude varies with loading conditions and heart rate

›Conditions that worsen LVOTO

›Reduced preload (dehydration, vasodilation, diuretics, standing)

›Reduced afterload (vasodilators, hypotension)

›Increased contractility (inotropes, tachycardia, catecholamines)

›Conditions that improve LVOTO

›Increased preload (IV fluids, leg raise, squatting)

›Increased afterload (phenylephrine, squatting, handgrip)

›Decreased contractility (beta-blockers, CCBs, cardiac myosin inhibitors)

›Diastolic dysfunction

›Impaired LV relaxation due to hypertrophied, stiff myocardium

›Elevated LV filling pressures despite normal or hyperdynamic EF

›Exertional dyspnea from increased pulmonary venous pressure

›Decreased LV end-diastolic volume from reduced chamber size

›Myocardial ischemia mechanisms

›Microvascular dysfunction: compressed intramural arterioles from hypertrophy

›Increased oxygen demand from hypertrophy and elevated wall stress

›Myocardial bridging: systolic compression of epicardial coronaries

›Subendocardial ischemia most common distribution

›Myocyte disarray and fibrosis

›Pathologic hypertrophy with disorganized myofibril arrangement

›Interstitial and replacement fibrosis: substrate for arrhythmia

›Late gadolinium enhancement on CMR represents replacement fibrosis

›Fibrosis extent correlates with arrhythmia burden and SCD risk

Therapeutic Considerations

›Pharmacologic goals in obstructive HCM

›Reduce LVOT gradient by decreasing contractility and HR

›Improve diastolic filling by prolonging diastolic interval

›Avoid worsening preload or afterload reduction

›Cardiac myosin inhibitors directly target the sarcomere hypercontractility mechanism

›Drug classes that worsen HOCM: absolute avoidance

›Vasodilators: nitrates, ACE inhibitors, ARBs, dihydropyridine CCBs

›Reduce afterload, worsening LVOTO and causing hemodynamic collapse

›Positive inotropes: dobutamine, dopamine, digoxin, milrinone

›Increase contractility, worsening obstruction and arrhythmia risk

›High-dose diuretics: excessive preload reduction precipitates collapse

›Stimulant medications and decongestants: catecholaminergic stimulation

›Anticoagulation principles in HCM

›AF anticoagulation mandatory regardless of CHA2DS2-VASc score

›LV apical aneurysm: anticoagulation recommended given thrombus risk

›Anticoagulation does not reduce SCD risk (different mechanism)

›Physical activity and lifestyle

›Moderate-intensity recreational exercise is safe and beneficial in most HCM patients

›Competitive sports: individualized risk discussion; 2024 guidelines allow shared decision-making

›Adequate hydration critical to maintain preload

›Avoid sudden intense exertion, especially in extreme heat

›Alcohol avoidance or strict limitation (vasodilatory and arrhythmogenic effects)

›Emerging therapies and research

›Cardiac myosin inhibitors (mavacamten, aficamten): first disease-modifying therapy class

›EXPLORER-HCM (mavacamten 2020): significant gradient and symptom reduction

›SEQUOIA-HCM (aficamten 2024): positive primary endpoint

›ACAMARA (aficamten 2025): non-inferior to metoprolol monotherapy

›Gene therapy in early stage research for sarcomere gene variants

›Antisense oligonucleotide therapy targeting MYBPC3 haploinsufficiency under investigation

11Patient Discharge Instructions/pdi44

copy discharge instructions

›Condition overview

›Your heart muscle is abnormally thickened (hypertrophic cardiomyopathy), causing a narrowing in the outflow tract of your heart

›This narrowing gets worse with dehydration, sudden positional changes, or stimulant drugs

›Your medications help relax the heart muscle and slow your heart rate to reduce this blockage

›Medications to take as prescribed

›Beta-blocker or calcium channel blocker: do not stop suddenly

›Stopping abruptly can cause dangerous rebound increase in heart rate and symptoms

›Take at the same time each day with or without food as directed

›If prescribed a cardiac myosin inhibitor (mavacamten or aficamten): take once daily

›Requires regular echocardiogram checks to monitor heart function

›Do not skip monitoring appointments

›If prescribed anticoagulation (blood thinner) for atrial fibrillation: take every day

›Do not stop without discussing with your doctor

›Report any unusual bleeding immediately

›Medications and substances to AVOID

›Blood pressure drugs that cause vasodilation: amlodipine, nifedipine, nitroglycerin, hydralazine

›Heart pump strengtheners (inotropes): digoxin, dobutamine

›Large doses of water pills (furosemide, hydrochlorothiazide) without cardiology guidance

›Stimulant medications: ADHD medications (amphetamines), decongestants (pseudoephedrine)

›Excessive caffeine and alcohol

›Lifestyle instructions

›Drink adequate fluids every day; avoid becoming dehydrated

›Increase fluid intake in hot weather, during illness, or with exercise

›Avoid large heavy meals that can worsen symptoms

›Do not perform intense competitive athletic activities unless cleared by your cardiologist

›Moderate recreational exercise is generally safe with guidance from your cardiologist

›Maintain a healthy weight and avoid smoking

12References/r39

Guidelines and key sources

›2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy

›Ommen SR, Ho CY, Asif IM, et al. Journal of the American College of Cardiology. 2024

›doi: 10.1016/j.jacc.2024.02.014

›Comprehensive guideline covering diagnosis, treatment, SCD risk, and special populations

›Braunwald E. Hypertrophic Cardiomyopathy. New England Journal of Medicine. 2025

›NEJM review covering pathophysiology, genetics, clinical features, and stepwise management

›doi: 10.1056/NEJMra2413445

›Maron BJ, Desai MY, Nishimura RA, et al. Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. JACC. 2022

›Practical guidance on pharmacotherapy, septal reduction therapy, and ICD indications

›PMID: 35086661

›Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. JACC. 2022

›Diagnostic criteria, imaging, genetic testing, and SCD risk stratification

›PMID: 35086660

Landmark trials

›EXPLORER-HCM Trial: mavacamten for symptomatic obstructive HCM

›Significant reduction in LVOT gradient and improvement in NYHA class vs placebo

›Supported FDA approval of mavacamten (Camzyos) in 2022

›SEQUOIA-HCM Trial: aficamten for symptomatic obstructive HCM

›Positive primary endpoint; supported FDA approval of aficamten (Myqorzo) in 2025

›ACAMARA Trial: Garcia-Pavia P, Maron MS, Masri A, et al. NEJM. 2025

›Aficamten monotherapy non-inferior to metoprolol for LVOT gradient reduction

›doi: 10.1056/NEJMoa2504654

›Dybro AM, Rasmussen TB, Nielsen RR, et al. Randomized Trial of Metoprolol in Obstructive HCM. JACC. 2021

›Randomized evidence supporting metoprolol for symptom relief in obstructive HCM

›PMID: 34915981

Additional references

›Sikand N, Stendahl J, Sen S, Lampert R, Day S. Current Management of Hypertrophic Cardiomyopathy. BMJ. 2025

Evidence & Review