Prof. N. Sudhaya Kumar,

AIMS, Cochin

Primary cardiomyopathies

Genetic

HCMARVD

LV noncompactionMitochondral myopathy

Glyc.storage dis.channelopathies

Mixed

DCMRCM

Acquired

InflammatoryTachycardiomyopathy

TakotsuboInfants of IDDM mothers

HCM

Most common of the genetic CVD

Mutation in genes coding proteins of sarcomere

Autosomal dominant pattern of inheritance

Heterogenous manifestation

Unique pathophysiology

Diverse clinical course

HCM

• most common cause of SCD in children

•30 % of SCD in competitive athletes

• LVH is a dynamic process

• occasionally LVH appears at or slightly after birth

• striking increase in LVH during adolescence

HCM .. GENETICS

• autosomal dominant

• usually missense mutations in genes that encode sarcomere proteins

• HCM mutant proteins are incorporated into cardiac myofilaments

• 50% of first degree relatives are at risk of inheriting the mutation

Hypertrophy, remodeling, fibrosis, dysfunction

HCM .. GENETICS

Mutations

missense, deletions,insertions,nonsense

Inthick filament proteins

thin filament proteins

metabolic genes

lysosomal proteins

HCM .. GENETICS

Protein chrom gene incidence clinical

Thick filament

BMHC 14 MYH7 40% classical HCM?regression with statin

MYBPC 11 MYBPC3 40% mild LVH, older age,good prognosis

Titin 2 TTN rare typical HCM

Thin filament

TropT 1 TNNT2I 5% modest LVH ; high SCD? Benefit with losartan/

spirono

Trop I 19 TNNI 3 rare ?apical ; restrictive physio

Actin 15 ACTC rare ? Apical

Tropomyosin 15 TPM 1 < 5% variable degree LVHgood prognosis> in Finland

HCM .. Classification (Maron’s)

Type 1 ..Hypertrophy confined to anterior IVS … 10%

2 .. Hypertrophy involving ant. & inferior IVS.. 20%

3 .. ,, IVS and lateral free wall 52%

4 .. ,, regions other than IVS 18%

5 .. Apical HCM

HCM -- Pathophysiology

• LV diastolic dysfunctionpulm. congestion

• LV outflow obstructiondynamicSAM , hypercontractile septum

• myocardial ischemiainadequate capillary densityabnormal microvasculaturemyocardial bridging of coronaries

• arrhythmiaischemia ; LVH ; fibrosis ; cardiac failure

HCM .. Clinical

Asymptomatic / symptomatic .. Dyspnea, angina, SCD..

Pulse .. brisk, spike and dome pattern

JVP .. A +

Apex .. Double / triple

Murmurs .. LVOT / MR

any situation which reduces LV size increases the

obstruction

Apex cardiogram in HOCM

Normal HOCM

ACG

ACG

HCM .. hemodynamics

HCM – Natural history

• presentation at any age

• overall mortality - 1% per year ; in children 2%

• SCD -- more in adolescence and young adults rare < 10 yrs extremely uncommon in infancy commonly arrhythmia based - VT / VF

> in early morning hourssedentary / modest activityduring or just after vigorous activity

HCM .. risk factors for SCD

• prior cardiac arrest / sustained VT

• family h/o HCM related SCD

• syncope

• repetitive nonsustained VT

• massive LVH > 30 mm

• fall in BP during exercise

• malignant genotype• LVOT gr > 50 mm Hg• myocardial ischemia• AF• competitive physical exertion

Major

Possible

HCM -- Management

• Pharmacologicbetablockers, verapamil , disopyramideantiarrhythmics .. ? Amiodaroneanticoagulationantifailure measures

• Pacing

• PTSA

• ICD

• Surgery

HCM …. Pacing

DDD pacing …. ? Benefit

2 randomised studies

Pacing In Cardiomyopathy trial …. Similar data

Conclusion : can be an option for severely symptomatic patients refractory to medical treatment and not planned for other treatment modalities

• modest reduction in LVOT gr . 25 – 40 mm Hg• subjective improvement• treadmill time / max. O2 cons. didn’t improve? Placebo effect

HCM -Surgery

• for patients with drug refractory symptoms and LVOT gradient of > 50 mm Hg

• septal resection (Morrow procedure)

• operative mortality < 1% ; 0% in Mayo series

• in 90% - abolition / reduction in LVOT gr

• in 85% - symptom relief

• 83 % 10 year survival

HCM -- PTSA

1 – 3 ml of 96 –98 % alcohol is injected intothe septal artery

Necrosis and thinning of IVS

Reduction in LVOT gradient

• scar may enhance arrhythmic death• high incidence of heart block• procedure mortality of 2%

Hence surgery is preferred in children

HCM … PTSA Vs surgery

myectomy PTSA

Procedure mortality 1 – 2 % 1 – 2 %

Gr. reduction (rest) to < 10mm Hg to < 25 mm Hg

Symptoms less less

PPI for AVB 1 – 2 % 5 – 10 %

Intramyocardial scar absent present

Longterm SCD risk very low ?

HCM … PTSA Vs surgery

CMR after myectomy Vs PTSA

HCM ..Prevention of SCD

• drugs -- ? Role

• ICD -- for primary and secondary prevention

Primary … > 1 major risk factor

Secondary .. SCD / sustained VT

• study of 128 ptsappropriate shock in 11%in secondary prevention and5% in primary prevention

HCM .. management

HCM SCD risk high … ICDAsymptomatic Follow up

Progressive symptoms

DRUGS BB ,verapamil, disopyramide

AF………cardioversion,rate control anticoagulation

paroxysmal AF.. ? amiodarone

Refractory

Nonobstructive obstructive

Tt of CHF Surgery … PTSAHeart transplant ?? DDD

HCM - screening

< 12 years – optional unlessfamily h/o HCM deathcompetitive athletessymptomatic

12 – 18 years -- every 12 –18 months

> 18 years -- every 5 years

HCM Athletes heart

Unusual pattern of LVH + _

LV cavity > 55 mm _ +

LA enlargement + _

Bizarre ECG + _

Abnormal LV filling ++ ±

LVH regression with _ +deconditioning

Family h/o ++ _

HCM Vs athletes heart