Prof. N. Sudhaya Kumar, AIMS, Cochin

1. HYPERTROPHIC CARDIOMYOPATHY Prof. N. Sudhaya Kumar, AIMS, Cochin

2. Primary cardiomyopathies Acquired Inflammatory Tachycardiomyopathy Takotsubo Infants of IDDM mothers Genetic HCM ARVD LV noncompaction Mitochondral myopathy Glyc.storage dis. channelopathies Mixed DCM RCM

3. 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

4. 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

5. 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

6. HCM .. GENETICS Mutations missense, deletions,insertions,nonsense In thick filament proteins thin filament proteins metabolic genes lysosomal proteins

7. 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 LVH good prognosis > in Finland

8. 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

9. HCM -- Pathophysiology • LV diastolic dysfunction • pulm. congestion • LV outflow obstruction • dynamic • SAM , hypercontractile septum • myocardial ischemia • inadequate capillary density • abnormal microvasculature • myocardial bridging of coronaries • arrhythmia • ischemia ; LVH ; fibrosis ; cardiac failure

10. 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

11. Apex cardiogram in HOCM ACG ACG Normal HOCM

12. HCM .. hemodynamics

14. 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 hours • sedentary / modest activity • during or just after vigorous activity

15. 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

16. HCM -- Management • Pharmacologic • betablockers, verapamil , disopyramide • antiarrhythmics .. ? Amiodarone • anticoagulation • antifailure measures • Pacing • PTSA • ICD • Surgery

17. 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

18. 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

19. HCM -- PTSA 1 – 3 ml of 96 –98 % alcohol is injected into the 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

20. 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 ?

21. HCM … PTSA Vs surgery CMR after myectomy Vs PTSA

22. HCM ..Prevention of SCD • drugs -- ? Role • ICD -- for primary and secondary prevention • Primary … > 1 major risk factor • Secondary .. SCD / sustained VT • study of 128 pts • appropriate shock in 11% • in secondary prevention and • 5% in primary prevention

23. HCM .. management HCM SCD risk high … ICD Asymptomatic Follow up AF………cardioversion,rate control anticoagulation paroxysmal AF.. ? amiodarone Progressive symptoms DRUGS BB ,verapamil, disopyramide Refractory Nonobstructive obstructive Tt of CHF Surgery … PTSA Heart transplant ?? DDD

24. HCM - screening < 12 years – optional unless family h/o HCM death competitive athletes symptomatic 12 – 18 years -- every 12 –18 months > 18 years -- every 5 years

25. HCM Vs athletes heart 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 ++ _

26. THANK YOU